Vietnamese Indigenous Medicinal Herbs: A New Approach for Antiviral Therapy and Post-COVID-19 Memory Protection

Paramignya trimera (locally known as Xáo tam phân) is a woody shrub from the citrus family Rutaceae, predominantly found in Khanh Hoa province, Vietnam. Traditionally, the roots of this herb are used to treat liver diseases, especially ascitic cirrhosis. The main chemical constituents in the roots of Paramignya trimera include coumarins and coumarin glycosides such as ostruthin, ninhvanin, and paratrimerin A and B.

Paramignya trimera (Xáo tam phân) – Photo by Nguyen Manh Cuong

The COVID-19 pandemic and the emergence of new SARS-CoV-2 variants have created an urgent need for new treatment methods alongside vaccines. In the human body, ACE-2 plays an important role in regulating blood pressure and fluid balance. It helps convert certain substances that affect blood vessels, thereby promoting vasodilation and reducing inflammation. However, ACE-2 is also the "gateway" used by SARS-CoV-2 to attach to and enter human cells via the spike (S) protein. Therefore, blocking ACE-2 activity could help prevent the virus from entering and developing in the body. As such, identifying natural compounds from medicinal plants that can inhibit the interaction between SARS-CoV-2 and ACE-2 receptors is drawing significant research attention as a promising therapeutic strategy.

Moreover, compounds with immunomodulatory and anti-inflammatory properties are also being studied to prevent the "cytokine storm" - the main cause of multi-organ damage in COVID-19 patients. Recent studies have also revealed a link between prolonged inflammation in the brain and the risk of post-COVID-19 memory loss. About 60–80% of patients exhibit symptoms of cognitive decline, with Vietnam reporting a rate of 65.8% among mild cases (data from Hanoi Medical University).

In light of this, Prof. Dr. Nguyen Manh Cuong and the research team from the Institute of Chemistry – Vietnam Academy of Science and Technology have carried out the project titled: “Evaluation of Anti-inflammatory and SARS-CoV-2 Inhibitory Effects of Potential Compounds Extracted from Vietnamese Medicinal Plants” (code: KHCBSS.01/21-23). The project aimed to isolate and evaluate natural compounds with promising biological activity, particularly their ability to inhibit SARS-CoV-2, provide anti-inflammatory effects, and protect nerve cells.

Prof. Dr. Nguyen Manh Cuong in the laboratory

Guided by the aim to study medicinal plants capable of affecting the ACE-2 receptor—the target of SARS-CoV-2 during human infection—the team isolated four new bis-coumarin glycosides: cis-paratrimerin A, B and trans-paratrimerin A, B (1–4) from the roots of Paramignya trimera in Khanh Hoa, Vietnam. These compounds were separated using conventional column chromatography, Sephadex chromatography, reverse-phase chromatography, and high-performance liquid chromatography (HPLC). Among them, cis-paratrimerin B (1) and cis-paratrimerin A (2) demonstrated ACE-2 inhibition in vitro with IC₅₀ values of 28.9 μM and 68.1 μM, respectively. Additionally, both aqueous and ethanol extracts from Paramignya trimera roots also showed ACE-2 inhibition in vitro.

Using computer-based simulation methods, the four biscoumarin glycosides—cis-paratrimerin A, B and trans-paratrimerin A, B (1–4)—exhibited high binding affinity to ACE-2 protein (with ΔG values of −14.70, −12.95, −11.94, and −10.69 kcal/mol). These biscoumarin glycosides from Paramignya trimera are potential ACE-2 inhibitors that warrant further study in the treatment of virus-related diseases, especially COVID-19. This is the first study to assess in vitro and in silico ACE-2 inhibitory effects of Vietnamese medicinal plants for the purpose of COVID-19 prevention and treatment (Nguyen Xuan Ha et al., Chem. Pharm. Bull., 2024).

Roots of Paramignya trimera and structures of new compounds cis-paratrimerin B (1) and cis-paratrimerin A (2)

According to Prof. Dr. Nguyen Manh Cuong, in patients infected with SARS-CoV-2, the "cytokine storm" syndrome is the main cause of excessive inflammation, worsening disease progression, and leading to multi-organ damage. Discovering natural compounds with strong anti-inflammatory properties from indigenous medicinal plants is considered a promising research direction in disease support and treatment.

In this project, the team recorded notable results in identifying anti-inflammatory properties from several Vietnamese medicinal plants. Specifically, they identified five plant extracts with strong anti-inflammatory effects, including: Rheum officinale (rhubarb), the branches and leaves of Dysoxylum tpongense, roots of Morinda longissima, rhizomes of Pinus krempfii (Krempf pine), and seeds of Passiflora edulis (purple passion fruit).

Moreover, extracts from Morinda longissima roots and purple passion fruit seeds were highly appreciated in both scientific research and pharmaceutical application potential. These two extracts require further research to develop into medications for inflammatory and neurodegenerative diseases, particularly for protecting nerve cells.

In animal testing, the ethanol extract from Morinda longissima roots (MLE) showed strong anti-inflammatory effects in mice. Chemical composition analysis using HPLC-HR-MS identified major compounds in the extract as anthraquinone and anthraquinone glycosides. Computer simulations revealed that these compounds can inhibit the COX-2 enzyme—a key player in triggering inflammatory responses in the body (Hafidha Mehallah, Nguyen Manh Cuong et al., Journal of Ethnopharmacology, 2024).

Additionally, the team discovered that extracts rich in stilbene compounds from purple passion fruit seeds contained a total phenolic content of 413.87 ± 1.71 mg GAE/g. Major compounds included trans-piceatannol, scirpusins A and B, and cassigarol. When tested at doses of 100 and 200 mg/kg, the extract showed effectiveness in reducing oxidative stress and brain inflammation while protecting nerve cells in a mouse model of neurodegeneration induced by D-galactose and AlCl₃.

Simulations also showed that two notable stilbene compounds—cassigarol E and scirpusin A—had strong inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes associated with memory loss disorders (Nadjet Mostefa, Nguyen Manh Cuong et al., Chemistry and Biodiversity, 2023).

During the implementation of this project, the team published five international papers (one in a SCI Q1 journal and four in SCIE-indexed journals), two national papers, registered two utility solutions with accepted valid applications, and contributed to training two graduate students.

The research results have paved a new way for utilizing agricultural by-products such as passion fruit seeds in developing anti-inflammatory and neuroprotective drugs. At the same time, this research supports the treatment of memory loss-related diseases, especially in post-COVID-19 patients.

Prof. Dr. Nguyen Manh Cuong (far left) with Mongolian partners and the research team in the laboratory

Prof. Dr. Nguyen Manh Cuong particularly emphasized the great potential of medicinal plants such as Paramignya trimera, Morinda longissima, and Passiflora edulis—species with abundant reserves and strong bioactivity. He believes that further studies are needed to understand their anti-inflammatory, antiviral, and neuroprotective mechanisms, with the ultimate goal of developing community health-protecting products based on Vietnam’s valuable natural resources.

Translated by Phuong Ha
Link to Vietnamese version