Homegrown solutions in Viet Nam: bringing C. asiatica compounds forward as candidates to treat liver cancer

Lead Research Organisation: University of Kent
Department Name: Sch of Physical Sciences

Abstract

Liver cancer is a critical problem in Viet Nam, killing 25 thousand Vietnamese individuals each year - more than any other cancer. The problem is especially acute in Viet Nam because of the convergence of overlapping risk factors: hepatitis B and C are prevalent; alcohol consumption is very high; dioxins persist in the environment stemming from the use of Agent Orange during the Viet Nam War; and cultural and economic factors mean that patients frequently present for modern medicine only at a very advanced stage, relying first on traditional herbal remedies.
However, Viet Nam also presents unique opportunities. Its traditional medicine is largely empirical i.e. based on experience rather than philosophical convictions. There is therefore opportunity for the discovery of natural products with therapeutic efficacy, which could be developed as approved drugs in an informed way through chemistry and biology. Centella asiatica is a popular medicinal herb, and our Vietnamese partners have discovered that one of its natural products, madecassic acid, is active against liver cancer, with chemical derivatives showing further improved potential.
In this project we will work on a number of fronts to bring madecassic acid derivatives forward as potential new therapeutics against liver cancer, which could be produced within Viet Nam. This involves optimisation of growth conditions for maximal madecassic acid production (using analytical chemistry), improvement of chemical extraction processes, broadening the range of chemical derivatives in hand, in-depth studies using chemical biology of the cellular effects of madecassic acid, and exploration of use of polymers to control the rate of release in the body. This work will be underlined and supported by networking activities with stakeholders (doctors, industrialists, farmers, policy makers) in Viet Nam, and survey work to assess attitudes of the population to medicines which cross over the traditional-modern divide.

Planned Impact

The impact of this work is oriented towards the benefit of Viet Nam in accordance with the UN's Sustainable Development Goals (SDGs). To ensure that these impacts are always kept in focus, we have assembled an Advisory Board comprised of representatives of the major stakeholders in Viet Nam, including a cancer clinician, the general director of a Vietnamese pharmaceutical company, the director of the farming cooperative in Hue province with whom we will work, and a regional politician. We will also have on our Advisory Board scientists from the UK who are involved in the plant-to-drug pipeline at all stages, along with a UK-based liver cancer clinical expert. This team, as well as further stakeholders, will be invited to workshops in the UK and Viet Nam to ensure maximal impact.
We will generate healthcare impact (SDG3) through research towards the development of drugs for liver cancer, which is the most pressing healthcare need in Viet Nam. To bring the drug to clinical trials and to market is a long term goal which extends beyond this grant, but we will ensure that this is always in mind, assisted by the advisory board, as well as the successful experience of Prof Sung and Prof Garrett in the discovery, development and clinical approval of drugs.
We will create economic impact (SDG1, 8, 9) in the short term by providing farmers in Hue province, a very poor area of Viet Nam, with the capacity to produce and extract Centella asiatica in much higher quantities; there is a very large market for these products in Viet Nam and across southeast Asia. In the longer term, they will be involved in producing the starting materials for any molecule which progresses from this project into an approved drug - this means that the opportunity for industry and innovation surrounding the production of a new drug will be centred on the poorest of the country. In the long term we will also improve Viet Nam's economic situation by reducing the financial burden of treatment of liver cancer which puts many families in serious hardship.
Environmental impact (SDG15) will be generated through development of organic farming practices, and social and political impact (SDG3, 10) will be produced by quantifying the extent to which drugs which cross the tradition/modern medicine divide will be seen favourably by the people of Viet Nam. We will also build capacity in Viet Nam for further research through consolidation of this partnership. Gender equality (SDG5) has been taken fully into account, with the majority of the project partners being women, equality being considered in recruitment, and both men and women being consulted equally in the survey component. Although liver cancer is more common in men than women in Viet Nam, the production of a new treatment will provide benefits to the whole of society.
All of these impacts complement the conventional academia and innovation aspects which are also encompassed within this work.
 
Description We have measured the content of bioactive molecules in the herb Centella asiatica, and determined the best time of year for growth and harvest, and optimised extraction conditions for these compounds. These results are being written up for publication.
We have conducted structure-activity relationship studies on madecassic acid, one of these bioactive compounds, and determined which positions on the molecule can be modified without altering its activity against liver cancer cells, and identified conjugates with silybin (which can protect the liver) which also retain activity. We have used this information to create a modified form of the compound which forms a permanent bond with any protein with which it interacts. We have performed proteomics and have a ranked list of proteins to examine in finer detail for the next step along the drug discovery pipeline.
We have conducted a survey on attitudes towards modern vs. traditional medicine in Vietnam. Our quantitative evidence is being prepared for publication.
Exploitation Route Centella asiatica is grown as a medicinal herb, so our findings will influence the practice of farmers more broadly.
Our structure-activity relationships and target ID will inform others developing drugs based upon madecassic acid.
The survey results will be shared with policy makers and healthcare professionals, and used to influence practice.
Sectors Agriculture

Food and Drink

Chemicals

Healthcare

Pharmaceuticals and Medical Biotechnology

URL https://research.kent.ac.uk/uvcap/
 
Description The project has contributed to the Sustainable Development Goals in: - SDG3: Good Health and Wellbeing. We have contributed to the planning of development policies on health protection supplements from Vietnam native plants. We have provided evidence that organic farming is economically viable for the commune farm with which we work and this has reduced their use of agrochemicals which impact their health - SDG8: Decent Work and Economic Growth. The project is payed portions of the wages of CoIs, RCoIs, farmers, and a social science expert in Viet Nam. They have received training and opportunities to advance their careers - SDG9: Industry, Innovation, and Infrastructure. The project is enabling the team at VAST to pursue new lines of scientific enquiry. We hasve shared results with Thua Thien Hue Pharmaceutical Enterprise with whom we will collaborate on further exploitation of results. There is currently a cosmetic cream in development - SDG15: Life on Land. We are testing the efficacy of organic fertiliser and time of year on production of our plant in a large plot in rural Viet Nam. Our results are being communicated to farmers who will thus be enabled to better protect the environment by creating a circular economy (reusing residue from extraction as fertiliser) Comparison to Gender Equality Statement: 1. Opportunities for Involvement. The gender balance of the management team remains. In recruitment, equality processes were adhered to, and outcome is that the UK-based PDRA is male, while the Viet Nam-based social science expert is female. Recruitment at all levels adhered to gender equality principles. 2+3. Primary impact dependent upon scientific findings (development of a drug) has not yet occurred - this will take many years and multiple grants. The Workpackage addressing cultural issues including gender (WP6) through social science has been completed and publication is in progress - these results will be shared with our network in the hospital and government in Viet Nam. 4. Gender officers were in place, and their comments welcomed and acted upon. 5. Measurement of gendered effects upon outcomes were taken into account through WP6.
First Year Of Impact 2020
Sector Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural

Economic

Policy & public services

 
Description Organic farming policy in Quang Tho II
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Contribution to new or improved professional practice
Impact The farmers report better wellbeing when not using agrochemicals.
 
Description Engaging with agriculture in Viet Nam for production of madecassic acid, a basis for a new liver cancer drug
Amount £5,000 (GBP)
Funding ID C23-7513697179 
Organisation Royal Society of Chemistry 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2024 
End 12/2024
 
Description GCRF and Newton Consolidation Account
Amount £150,000 (GBP)
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 08/2022 
End 03/2023
 
Description Partnership for antimicrobial studies 
Organisation University of Kent
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided the set of modified madecassic acid compounds used to discover structure-activity relationships as part of the project to Dr Mark Shepherd and Dr Becky Hall, both of the Kent School of Biosciences.
Collaborator Contribution The new partners have begun testing the compounds against bacterial and fungal pathogens, and there are some promising results.
Impact A list of antimicrobial activities compared with structural features on the molecule.
Start Year 2022
 
Description Partnerships in original application 
Organisation Asian Management and Development Institute (AMDI)
Country Viet Nam 
Sector Private 
PI Contribution The work is a collaboration between the University of Kent (Dr Christopher Serpell, Prof Michelle Garrett, Dr Rebecca Cassidy), and institutions in Viet Nam, the DAC list partner country: Prof Sung Van Tran, Dr Thao Thi Do, Dr Thao Tran Thi Phuong, Dr Chien Tran Van (Vietnam Academy of Science and Technology), Dr Nhu Vo Thi Quynh (Gio Linh High School), and Ngo Cong Chinh (Asian Management and Development Institute). These individuals made up the executive board and are in charge of running the project. Ngo Cong Chinh has been replaced by Be Thi Hoang Yen at AMDI, and Nhu Vo Thi Quynh has left the project. We have also recruited an advisory board, consisting of both Vietnam- and UK-based individuals: Phan Thi Minh Tam (Pharmaceutical company Medipharco), Hoang Cong Phong (President of people committee of Quang Tho commune), Nguyen Luong Tri, director of cooperative Quang Tho Ii), Dr Hu Xuan Dung (Hue University for Medicine and Pharmacy), Dr Gurprit Lall (Medway School of Pharmacy), Dr Rohini Sharma (Imperial College London), Prof Mark Searcey (UEA), Dr Jose Prieto-Garcia (UCL), and Dr Alison Foster (Botanical Horticulturist and Science Communicator). I was in charge of WP2 (with Michelle Garrett) and WP4 of the research project, and am contributing chemical synthesis, as well as management of the overall project.
Collaborator Contribution WP1 was managed by Tran Van Sung and Thao Tran Thi Puong. WP3 was managed by Thao Thi Do and Tran Van Chien. WP5 was managed by Tran Van Sung. WP6 was managed by Rebecca Cassidy and Be Thi Hoang Yen. The Advisory Board participate in workshops and receive and comment upon regular reports.
Impact See 'Engagement Activities.' Two preprints are available (see publications). We have received further funding from the Royal Society of Chemistry (RSC Researcher Collaboration grant) for further development of the project.
Start Year 2020
 
Description Partnerships in original application 
Organisation University of Kent
Country United Kingdom 
Sector Academic/University 
PI Contribution The work is a collaboration between the University of Kent (Dr Christopher Serpell, Prof Michelle Garrett, Dr Rebecca Cassidy), and institutions in Viet Nam, the DAC list partner country: Prof Sung Van Tran, Dr Thao Thi Do, Dr Thao Tran Thi Phuong, Dr Chien Tran Van (Vietnam Academy of Science and Technology), Dr Nhu Vo Thi Quynh (Gio Linh High School), and Ngo Cong Chinh (Asian Management and Development Institute). These individuals made up the executive board and are in charge of running the project. Ngo Cong Chinh has been replaced by Be Thi Hoang Yen at AMDI, and Nhu Vo Thi Quynh has left the project. We have also recruited an advisory board, consisting of both Vietnam- and UK-based individuals: Phan Thi Minh Tam (Pharmaceutical company Medipharco), Hoang Cong Phong (President of people committee of Quang Tho commune), Nguyen Luong Tri, director of cooperative Quang Tho Ii), Dr Hu Xuan Dung (Hue University for Medicine and Pharmacy), Dr Gurprit Lall (Medway School of Pharmacy), Dr Rohini Sharma (Imperial College London), Prof Mark Searcey (UEA), Dr Jose Prieto-Garcia (UCL), and Dr Alison Foster (Botanical Horticulturist and Science Communicator). I was in charge of WP2 (with Michelle Garrett) and WP4 of the research project, and am contributing chemical synthesis, as well as management of the overall project.
Collaborator Contribution WP1 was managed by Tran Van Sung and Thao Tran Thi Puong. WP3 was managed by Thao Thi Do and Tran Van Chien. WP5 was managed by Tran Van Sung. WP6 was managed by Rebecca Cassidy and Be Thi Hoang Yen. The Advisory Board participate in workshops and receive and comment upon regular reports.
Impact See 'Engagement Activities.' Two preprints are available (see publications). We have received further funding from the Royal Society of Chemistry (RSC Researcher Collaboration grant) for further development of the project.
Start Year 2020
 
Description Partnerships in original application 
Organisation Vietnam Academy of Science and Technology
Country Viet Nam 
Sector Academic/University 
PI Contribution The work is a collaboration between the University of Kent (Dr Christopher Serpell, Prof Michelle Garrett, Dr Rebecca Cassidy), and institutions in Viet Nam, the DAC list partner country: Prof Sung Van Tran, Dr Thao Thi Do, Dr Thao Tran Thi Phuong, Dr Chien Tran Van (Vietnam Academy of Science and Technology), Dr Nhu Vo Thi Quynh (Gio Linh High School), and Ngo Cong Chinh (Asian Management and Development Institute). These individuals made up the executive board and are in charge of running the project. Ngo Cong Chinh has been replaced by Be Thi Hoang Yen at AMDI, and Nhu Vo Thi Quynh has left the project. We have also recruited an advisory board, consisting of both Vietnam- and UK-based individuals: Phan Thi Minh Tam (Pharmaceutical company Medipharco), Hoang Cong Phong (President of people committee of Quang Tho commune), Nguyen Luong Tri, director of cooperative Quang Tho Ii), Dr Hu Xuan Dung (Hue University for Medicine and Pharmacy), Dr Gurprit Lall (Medway School of Pharmacy), Dr Rohini Sharma (Imperial College London), Prof Mark Searcey (UEA), Dr Jose Prieto-Garcia (UCL), and Dr Alison Foster (Botanical Horticulturist and Science Communicator). I was in charge of WP2 (with Michelle Garrett) and WP4 of the research project, and am contributing chemical synthesis, as well as management of the overall project.
Collaborator Contribution WP1 was managed by Tran Van Sung and Thao Tran Thi Puong. WP3 was managed by Thao Thi Do and Tran Van Chien. WP5 was managed by Tran Van Sung. WP6 was managed by Rebecca Cassidy and Be Thi Hoang Yen. The Advisory Board participate in workshops and receive and comment upon regular reports.
Impact See 'Engagement Activities.' Two preprints are available (see publications). We have received further funding from the Royal Society of Chemistry (RSC Researcher Collaboration grant) for further development of the project.
Start Year 2020
 
Description Focus group discussions 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Focus group discussions (FGDs) have been conducted with cancer research scientists at the Vietnam Academy of Science and Technology, (10 individuals, 7:3 male:female), doctors at Vietnam National Cancer Hospital (6, 2:4), and patients at the same site (6, 4:2), and in-depth interviews have been conducted with pharmacists nearby Vietnam National Cancer Hospital and within the hospital pharmacy department (6, 2:4) and a herbalist at a traditional medicine shop on Thanh Cong street (1, male), all based in/around Hanoi, Vietnam. More in-depth interviews are due to occur, and the information gathered from these will be used to inform a full survey study.
This engagement activity is being conducted to ensure that our development of drugs based upon traditional Vietnamese plants creates products which are culturally acceptable within the country, and medically appropriate to the needs of Viet Nam.
Year(s) Of Engagement Activity 2021
 
Description Mid-project workshop (online) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A mid project workshop was held online on 11th Jan 2022, to share updates on the research project "Home-grown solutions in Viet Nam: Bringing C. asiatica compounds forward as candidate to treat livers cancer" It was attended by a total of 43 Vietnamese participants (20 male, 23 female) including invitees from industry, government and representatives of both users and prescribers (including medical doctors and pharmacists), as well as interested academics in the UK, Laos, and Malaysia. There were a total of 47 participants from Viet Nam, of whom 25 were male and 22 female. They were based at hospitals, pharmaceutical companies, agriculture cooperatives, and academia. The meeting was a remote event due to COVID restrictions in Vietnam at the time. There was a session in Vietnamese at which the updates were presented, followed by lively discussion. After that, there was an English language international session during which a video was presented (https://www.youtube.com/watch?v=jjf7HfgG4CI) and updates were again shared. Pleasingly, most of the Vietnamese contingent also stayed for the international session which extended into the evening in that country. Again there were lively questions and discussion. The following day, a closed-doors meeting was held with the project Advisory Board, at which the most important questions were discussed in greater depth, and plans made for the future.
Year(s) Of Engagement Activity 2022
URL https://www.youtube.com/watch?v=jjf7HfgG4CI
 
Description Project inception workshop, Hanoi 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A project kick-off workshop was held in Ha Noi on November 24, 2020, to introduce research project "Home-grown solutions in Viet Nam: Bringing C. asiatica compounds forward as candidate to treat livers cancer" It was attended by a total of 43 Vietnamese participants (20 male, 23 female) including invitees from industry, government and representatives of both users and prescribers (including medical doctors and pharmacists). The meeting was a hybrid live/videoconference, with British team members attending and presenting via Teams. A brief introduction to the research and its objectives was given, followed by lively questions from the attendees. A survey was conducted at the end of the meeting concerning the perception of the potential of the project to make a difference.

Representatives were present from: research agencies (VAST institutes of Chemistry, Natural Product Chemistry, Marine Biochemistry, and Biotechnology); Hue cooperative who produce the plant of interest in this study (Quang Dien DPC, Cooperative Quang Tho, Hue University of Medicine and Pharmacy, Hue Department of Science and Technology); the private sector (Traphaco, Mediplantec, Pangroup, Medipharco)
Year(s) Of Engagement Activity 2020
URL https://research.kent.ac.uk/uvcap/
 
Description Project networking trip 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The PI and CoIs from the UK visited Viet Nam in June 2022 to consolidate links and prepare for further work. We engaged with the National Cancer Hospital, the Quang Tho II farm, and the pharmaceutical industry, as well as the Vietnamese team of CoIs and Researcher CoIs, in Hanoi and in Hue.
Year(s) Of Engagement Activity 2022
URL https://research.kent.ac.uk/uvcap/visit-of-uk-team-to-viet-nam/
 
Description Summation workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A workshop was held in Hanoi to share results and discuss the future of the project. Clinicians, policymakers, farmers, representatives of patients' groups, and the media were present.
Year(s) Of Engagement Activity 2023
 
Description TV interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Brief interview on VTC14 News, from 7min 30sec in link.
Year(s) Of Engagement Activity 2023
URL https://www.youtube.com/watch?v=Z67ct_LZDfA