Min-Han Chi1†
Chien-Yu Ko1†
Ting-Wei Chi2
Chi-Ruei Huang3Jaung-Geng Lin4
Jung Chao5*
Shyh-Shyun Huang1,6*- 1School of Pharmacy, China Medical University, Taichung, Taiwan
- 2Department of Rehabilitation, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- 3School of Medicine, Tzu Chi University, Hualien, Taiwan
- 4School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- 5Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, Master Program for Food and Drug Safety, Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- 6Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan
Introduction: Traditional Chinese medicine (TCM) pharmacies in Taiwan have been a vital healthcare resource in Chinese communities, with generations of accumulated TCM knowledge playing a crucial role in infectious disease prevention and treatment. However, as proprietors age and the industry declines, this valuable ethnomedicinal knowledge faces the risk of being lost. Therefore, documenting and analyzing the knowledge used by Taiwanese TCM pharmacies in combating COVID-19 is essential for the preservation and application of ethnomedicine.
Methods: This study employed a stratified sampling method to survey 106 TCM pharmacies in Taiwan, collecting 61 TCM formulae against COVID-19. The medicinal materials were compiled, and analysis were conducted using relative frequency of citation (RFC) and the Phi correlation coefficient to examine the relationships among TCMs. Furthermore, cluster analysis was applied to establish TCM combination patterns.
Results: This study recorded a total of 70 medicinal materials and identified 30 commonly used ones, categorizing them into four major groups: Group A (heat-clearing and detoxifying): As similar as NRICM101, suitable for moderate to severe cases. Group B (heat-clearing and tonifying): Suitable for mild cases, with both antiviral and immune-boosting effects. Group C (symptom relief): Primarily used for relieving cough, expelling phlegm, and alleviating discomfort. Group D (tonifying and strengthening): Suitable for uninfected individuals to enhance immunity.
Discussion: This study successfully documented and analyzed the TCM usage patterns of Taiwanese TCM pharmacies in combating COVID-19, revealing their alignment with modern TCM theories. The findings not only contribute to the preservation of ethnobotanical knowledge but also serve as a reference for developing herbal prevention strategies and healthcare products, ensuring that traditional medical wisdom can play a greater role within the modern healthcare system.
1 Introduction
Coronavirus Disease 2019 (COVID-19) first emerged in Wuhan, China, in early December 2019 (Ahn et al., 2020; Zhou P. et al., 2020; Zhu et al., 2020). Research identified the pathogen as a novel coronavirus, named SARS-CoV-2 (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). According to statistics from the World Health Organization (WHO), as of 2 February 2025, the global number of confirmed COVID-19 cases has exceeded 770 million, with more than 7 million deaths (World Health Organization, 2024). Although the COVID-19 pandemic has gradually subsided with the increase in vaccination rates, studies have indicated that COVID-19 infection significantly raises the risk of cardiovascular complications and chronic kidney disease (Del Vecchio et al., 2024). Therefore, the search for potential drugs to prevent and treat COVID-19 infection remains important and necessary. According to the COVID-19 treatment guidelines published by the National Institutes of Health (NIH), recommended drugs for non-hospitalized adult patients include glucocorticoids (e.g., Dexamethasone), 3C-like protease inhibitors [e.g., Nirmatrelvir/ritonavir (Paxlovid®)], Nucleoside Analogues (e.g., Molnupiravir), and RNA-dependent RNA polymerase inhibitors (e.g., Remdesivir) (COVID-19 Treatment Guidelines Panel, 2024). The most used therapeutic drug in clinical settings is Paxlovid®. Although studies have shown that Paxlovid® can reduce the severity of COVID-19 symptoms, its high cost and potential for multiple drug interactions still make it unaffordable and intolerable for many patients with chronic diseases (Marzolini et al., 2022). In addition, the development of other new drugs takes a long time, which is not a quick solution. As a result, there has been an international effort to explore the therapeutic and preventive effects of traditional Chinese herbal medicine for COVID-19.
As countries worldwide strive to control the COVID-19 pandemic, the development of new drugs is time-consuming and cannot provide an immediate solution. Therefore, drug repurposing has become the primary strategy for using existing Western medicines to treat COVID-19 (Singh et al., 2020; Zhou Y. et al., 2020; Asselah et al., 2021; Yousefi et al., 2021). However, the side effects of many Western medicines are often difficult for patients to tolerate, and the therapeutic effects of drug repurposing remain limited. As a result, there has been a growing international effort to explore the therapeutic and preventive effects of traditional Chinese herbal medicine for COVID-19. A previous study tracked 782 patients who were treated with the traditional Chinese herbal formula—Qingfei Paidu Decoction (QFPDD)—for COVID-19. The findings revealed that early use of QFPDD significantly shortened the disease recovery period and hospitalization duration (Shi et al., 2020). Another systematic review found that the disease cure rate in the combined Chinese and Western medicine group was higher than that in the Western medicine-only group. Additionally, it was observed that the integration of Chinese and Western medicine significantly reduced the length of hospital stay for patients (Liu M. et al., 2020). In summary, the use of traditional Chinese herbal medicine alone or in combination with Western medicine can effectively shorten the COVID-19 recovery period. Therefore, exploring potential effective herbal medicines for the prevention and treatment of COVID-19 holds significant promise.
Previous studies have indicated that the annual prevalence of over-the-counter traditional Chinese medicine (TCM) purchases among the Taiwanese population is as high as 74.8% (Hu et al., 2020). According to statistics from the Ministry of Health and Welfare (MOHW) of Taiwan, as of the end of 2020, there were 8,348 TCM pharmacies across Taiwan (Ministry of Health and Welfare, 2024). On average, there are 0.231 TCM pharmacies per square kilometer, making them highly accessible. As a result, TCM pharmacies remain the primary channel for the Taiwanese public to purchase herbal medicines. These pharmacies have existed in Taiwanese society long before the introduction and development of Western medicine, with generations of accumulated TCM knowledge serving as a crucial tool for combating diseases in Chinese communities. Even today, despite the rapid advancement of Western medicine, the knowledge preserved in TCM pharmacies continues to play a vital role in disease prevention and health maintenance within Chinese society. Today, TCM pharmacies in Taiwan serve as rich repositories of TCM knowledge. However, the average age of TCM pharmacy proprietors has exceeded 60 years, and the number of pharmacies is decreasing annually. Therefore, exploring and preserving the extensive TCM knowledge passed down through these pharmacies has become an urgent task.
In this study, we conducted fieldwork to community TCM pharmacies in Taiwan, collecting the herbal formulae they offered for COVID-19 treatment. We analyzed these formulae, identified candidate medicinal materials used against COVID-19, and applied statistical analysis to examine the relationships between these medicinal materials. By doing so, we uncovered the selection patterns of medicinal materials used by TCM pharmacies in combating COVID-19. Ultimately, the findings of this study aim to provide clinical practitioners with reference data for COVID-19 treatment prescriptions and support the development and application of health products.
2 Materials and methods
2.1 Ethical review
This study was conducted from July 2021 to June 2022 and was approved by the Central Regional Research Ethics Committee of China Medical University and Hospital (Approval No. CMUH110-REC2-115) (Supplementary Figure S1).
2.2 Study area and formulae collection
The study area for this research is Taiwan, a spindle-shaped island located in the western Pacific Ocean, positioned between the Republic of the Philippines and the Ryukyu Islands. To the west, Taiwan is separated from the People’s Republic of China by the Taiwan Strait. According to the Taiwan Geodetic Datum 1997 (TWD97) coordinate system, the geographic reference point of Taiwan is (23°58′N, 120°58′E), with a total land area of approximately 36,000 km2.
The sampling data for this study were based on the official statistics published by the Department of Statistics at the MOHW in Taiwan (Ministry of Health and Welfare, 2024), using the data on the number of licensed TCM pharmacies operating under Article 103 of the Pharmaceutical Affairs Act as of the end of 2020, and stratified by county and city. The number of sampled pharmacies in each county and city was determined according to the distribution ratio presented in the official statistics (Supplementary Table S1).
After determining the sample size, the pharmacies in each county and city were visited to purchase the anti-COVID-19 formulae and the purchase information was recorded in detail (Figure 1). After reaching the estimated number of formulae to be collected in each county and city, the formulae were taken to the laboratory for disassembly.
Figure 1. Photograph of TCM pharmacy (A) Appearance of TCM pharmacy (B) TCM cabinet (C) Anti-COVID-19 handwritten prescription (D) Anti-COVID-19 formula (E) Distribution map of 106 TCM pharmacies. Note: The red dots represent the locations of successful collection pharmacies; the blue dots represent the locations of failed collection pharmacies. KEL, Keelung City; TPE, Taipei City; NTPC, New Taipei City; TYN, Taoyuan City; HSZ, Hsinchu County; ZMI, Miaoli County; TXG, Taichung City; CHW, Changhua County; NTC, Nantou County; YUN, Yunlin County; CYI, Chiayi County; TNN, Tainan City; KHH, Kaohsiung City; PIF, Pingtung County; ILA, Yilan County; HUN, Hualien County; TTT, Taitung County.
2.3 Medicinal material identification and information sorting
In this study, the macroscopical identification method was used during formulae disassembly and medicinal materials recognition (Supplementary Figure S2). Firstly, the identification of medicinal materials was conducted through visual, olfactory, gustatory, and tactile examination (Zhao et al., 2011). Secondly, image authentication was carried out against the “Taiwan Herbal Pharmacopeia Database” (Department of Chinese Medicine and Pharmacy, 2024) and the “Color Atlas for the Authentic and Superior Chinese Material Medica” (Xian-Zhe, 2007). Thirdly, the results of the secondary authentication were provided to a review panel consisting of three PhDs in traditional Chinese medicine and two practitioners in Chinese medicine industry. These five experts conducted tertiary authentication by double-checking the results of the secondary authentication, and authentication report was compiled to confirm the correct origin of the medicinal materials. Afterwards, the medicinal materials were then photographed using a smartphone, and detailed information for each formula was compiled into a digital report (PDF file) for recordkeeping. Finally, each formula was ultimately packed into a separate bag, with the purchase location and date handwritten on the bag, and stored at the specimen storage area in the China Medical University.
In order to include information about all the medicinal materials collected in this study, the study referred to the Taiwan Herbal Pharmacopeia fourth Edition (Taiwan Herbal Pharmacopeia 4th Edition Committee, 2021), the Pharmacopoeia of the People’s Republic of China 2020 Edition (Chinese Pharmacopoeia Commission, 2020), and Chinese Materia Medica (National Administration of Traditional Chinese Medicine “Chinese Materia Medica” Editorial Board, 1999) for medicinal material data collection. The collected information included kingdom, family, local name, scientific name, part used, traditional use, and property and flavor. If discrepancies exist among the three references, the hierarchy of information, from highest to lowest authority, is as follows: the Taiwan Herbal Pharmacopeia fourth Edition, the Pharmacopoeia of the People’s Republic of China 2020 Edition, and Chinese Materia Medica. For medicinal materials with differing family classifications and scientific names across different references, verification and standardization were conducted using World Flora Online database (Royal Botanic Gardens and Garden, 2024).
2.4 Data analysis
The data collected in this study were analyzed and visualized using Microsoft Office 365 Excel, GraphPad Prism (Version 10.2.2), Adobe Illustrator (Version 28.5.0.132), and RStudio (Version 2024.04.2). For quantitative analysis, two parameters were applied: relative frequency of citation (RFC) and the Phi coefficient. Referring to the RFC formula definition from previous studies (Ahmad et al., 2017), the formula was modified to fit this study, as shown below:
For the Phi coefficient, a contingency table was first created to record the occurrence frequency of any two medicinal materials. Then, referring to the Phi coefficient formula from previous studies (Chytrý et al., 2002; Cui et al., 2016), it was modified to fit this study, as shown below:
In this formula, “a” represents the number of formulae in which both TCM-A and TCM-B appear; “b” represents the number of formulae in which TCM-A appears but TCM-B does not; “c” represents the number of formulae in which TCM-A does not appear but TCM-B does; and “d” represents the number of formulae in which neither TCM-A nor TCM-B appear. The Phi coefficient ranges from −1 to +1, with higher values indicating stronger associations between the medicinal materials. The calculated Phi coefficient values were then combined with cluster analysis to generate a network graph, which was used to explore the combination patterns of medicinal materials in Taiwan TCM pharmacies for combating COVID-19.
3 Results
3.1 Results of anti-COVID-19 formulae and medicinal material information collection
According to the data published by the Department of Statistics at MOHW in Taiwan at the end of 2020, there were a total of 8,348 TCM pharmacies in Taiwan, operating in accordance with Article 103 of the Pharmaceutical Affairs Act. Among these, Kaohsiung City had the highest number of pharmacies, with 1,350, while Taitung County had the fewest, with only 48 (Supplementary Table S1). This study conducted stratified sampling based on counties and cities, with the sample size determined according to the proportion of TCM pharmacies in each area. A total of 106 pharmacies were randomly selected for fieldwork. As a result, 61 anti-COVID-19 formulae were successfully collected. Additionally, 45 pharmacies reported that they did not sell any anti-COVID-19 formula (Figure 1).
Differences in taxonomic methods and the specific versions applied during the compilation of different pharmacopeias have led to inconsistencies in classification. Therefore, for the families and scientific names, this study uses the content recorded in World Flora Online as the standard to correct and integrate the plant information from each pharmacopeia (Royal Botanic Gardens and Garden, 2024). In this study, among the 61 formulae, a total of 70 medicinal materials were identified. Of these, 1 medicinal material belongs to the Fungi kingdom (1.43%), while the remaining 69 medicinal materials belong to the Plantae kingdom (98.57%). These 70 medicinal materials are distributed across 40 families, with the most common families being the Lamiaceae (n = 8, 11.43%), Apiaceae (n = 6, 8.57%), Fabaceae (n = 4, 5.71%), and Compositae (n = 4, 5.71%). Statistical results of the parts used suggested that 17 medicinal parts are used, with the radix being the most common (n = 19, 27.14%), followed by the rhizoma (n = 11, 15.71%) (Supplementary Figure S3).
3.2 Properties, flavors, and traditional uses of medicinal materials against COVID-19
Each medicinal material may possess multiple medicinal flavors, but it will only have one medicinal property. Medicinal properties can be classified as hot, warm, neutral, cool, or cold; medicinal flavors can be classified as sour, bitter, sweet, pungent, salty, bland, and astringent. This study consolidates pharmacopeial information for 70 medicinal materials, with cold properties (41.43%) and warm properties (40.00%) being the most prevalent (Figure 2A). The medicinal flavors are predominantly sweet (34.86%), bitter (33.03%), and pungent (23.85%) (Figure 2B). When both medicinal flavors and properties are considered together, the most common combinations are bitter and cold (18.35%), pungent and warm (17.43%), and sweet and cold (15.60%) (Figure 2C). In terms of traditional uses, among the 70 medicinal materials consolidated in this study, the top three most common traditional uses are “Qi-tonifying” (14.29%), “Heat-clearing and detoxicating” (11.43%), and “Pungent-warm exterior-releasing” (11.43%) (Figure 2D).
Figure 2. Flavor, property and traditional use statistics analysis charts of 70 medicinal materials combating COVID-19 (A) Radar plot of properties (B) Radar plot of flavors (C) Correlation heat map of flavors and properties (D) Bar chart of traditional uses.
3.3 Correlation of medicinal materials against COVID-19
To determine the usage frequency of each medicinal material, this study calculated the RFC values for the 70 medicinal materials and excluded those with RFC values below 0.05 from the correlation statistics. Among the 70 medicinal materials, 30 had RFC values greater than 0.05 (referred to as commonly used medicinal materials), in descending order of Glycyrrhiza uralensis Fisch. (RFC = 0.574), Houttuynia cordata Thunb. (RFC = 0.475), Ziziphus jujuba Mill. (RFC = 0.459), Mentha canadensis L. (RFC = 0.361), Lycium chinense Mill. (RFC = 0.361), Astragalus mongholicus Bunge (RFC = 0.328), Hedysarum polybotrys Hand.-Mazz. (RFC = 0.311), Morus alba L. (RFC = 0.279), Lonicera japonica Thunb. (RFC = 0.230), Ophiopogon japonicus (Thunb.) Ker Gawl. (RFC = 0.197), Saposhnikovia divaricata (Turcz.) Schischk. (RFC = 0.180), Cinnamomum cassia (L.). J.Presl (RFC = 0.180), Platycodon grandiflorus (Jacq.) A.DC. (RFC = 0.180), Nepeta tenuifolia Benth. (RFC = 0.164), Perilla frutescens (L.). Britton (RFC = 0.148), Chrysanthemum morifolium Ramat. (RFC = 0.131), Codonopsis pilosula (Franch.) Nannf. (RFC = 0.131), Atractylodes macrocephala Koidz. (RFC = 0.115), Angelica sinensis (Oliv.) Diels (RFC = 0.115), Scutellaria baicalensis Georgi (RFC = 0.098), Panax quinquefolius L. (RFC = 0.098), Zingiber officinale Roscoe (RFC = 0.098), Trichosanthes kirilowii Maxim. (RFC = 0.082), Isatis tinctoria L. (RFC = 0.082), Ligusticum striatum DC. (RFC = 0.082), Agastache rugosa (Fisch. and C.A.Mey.) Kuntze (RFC = 0.082), Phragmites australis (Cav.) Trin. ex Steud. (RFC = 0.082), Panax ginseng C.A.Mey. (RFC = 0.082), Strobilanthes cusia (Nees) Kuntze (RFC = 0.066), and Citrus reticulata Blanco (RFC = 0.066) (Table 1).
Table 1. Information on 70 medicinal materials used in anti-COVID-19 formulae.
The Phi coefficient is a parameter used to measure the correlation between two binary variables. In this study, the occurrence of medicinal materials is considered a binary variable (either present or not present). To clarify the correlation between any two medicinal materials, this study calculates the occurrence of any two medicinal materials among the 30 commonly used medicinal materials in 61 medicinal formulae, constructs a frequency contingency table (Supplementary Table S2), and then calculates the Phi coefficient based on the results of the contingency table. Next, the Phi coefficient was combined with cluster analysis to create a network diagram (Figure 3). The results of the cluster analysis divided the 30 commonly used medicinal materials into four groups: Group A (N = 9) included G. uralensis, H. cordata, M. canadensis, M. alba, S. divaricata, N. tenuifolia, S. baicalensis, T. kirilowii, and S. cusia; Group B (N = 8) included A. mongholicus, L. japonica, C. cassia, A. macrocephala, Z. officinale, I. tinctoria, A. rugosa, and C. reticulata; Group C (N = 5) included O. japonicus, P. grandiflorus, P. frutescens, C. morifolium, and P. australis; Group D (N = 8) included Z. jujuba, L. chinense, H. polybotrys, C. pilosula, A. sinensis, P. quinquefolius, L. striatum, and P. ginseng.
Figure 3. Network diagram of 30 commonly used medicinal materials against COVID-19. Note, The lines indicate a positive Phi coefficient between two medicinal materials. Different colors represent different groups in the cluster analysis. AGR, A. mongholicus; AMR, A. macrocephala; ASR, A. sinensis; ATH, A. rugosa; CMR, C. cassia; CRP, C. reticulata; CSF, C. morifolium; CSR, C. pilosula; CXR, L. striatum; GLY, Glycyrrhiza uralensis; GSG, P. ginseng; HDR, H. polybotrys; HNH, H. cordata; ITR, Isatis tinctoria; JJB, Z. jujuba; LCF, L. chinense; LJF, L. japonica; MRF, M. alba; MTH, M. canadensis; NPH, Nepeta tenuifolia; OPR, Ophiopogon japonicus; PCR, P. grandiflorus; PLF, P. frutescens; PMR, P. australis; PQR, P. quinquefolius; SCR, S. cusia; SKE, S. divaricata; STR, S. baicalensis; TSF, Trichosanthes kirilowii; ZGB, Z. officinale.
3.4 Dosage of medicinal materials against COVID-19
In this study, based on the calculation results of Louvain community detection model, the 30 commonly used medicinal materials against COVID-19 were divided into four groups (Figure 4). In Group A, the dosage distribution ranged from 1.5 g to 45.0 g. The highest average dosage was S. cusia (15.3 g), while the lowest average dosage was N. tenuifolia (9.3 g). The medicinal material with the largest dosage range was M. canadensis (3.8 g–45.0 g). In Group B, the dosage distribution ranged from 1.0 g to 61.9 g. The highest average dosage was A. mongholicus (17.9 g), while the lowest average dosage was A. rugosa (5.8 g). The medicinal material with the largest dosage range was C. cassia (2.0 g–61.9 g). In Group C, the dosage distribution ranged from 1.0 g to 20.0 g. The highest average dosage was O. japonicus (9.3 g), while the lowest average dosage was P. australis (6.0 g). The medicinal material with the largest dosage range was P. grandiflorus (1.0 g–20.0 g). In Group D, the dosage distribution ranged from 1.0 g to 71.0 g. The highest average dosage was Z. jujuba (25.5 g), while the lowest average dosage was L. striatum (5.7 g). The medicinal material with the largest dosage range was Z. jujuba (2.0 g–71.0 g).
Figure 4. Boxplot of dosages for commonly used medicinal materials against COVID-19 (A) Group A (N = 9) (B) Group B (N = 8) (C) Group C (N = 5) (D) Group D (N = 8). AGR, A. mongholicus; AMR, A. macrocephala; ASR, A. sinensis; ATH, A. rugosa; CMR, C. cassia; CRP, C. reticulata; CSF, C. morifolium; CSR, C. pilosula; CXR, L. striatum; GLY, Glycyrrhiza uralensis; GSG, P. ginseng; HDR, H. polybotrys; HNH, H. cordata; ITR, Isatis tinctoria; JJB, Z. jujuba; LCF, L. chinense; LJF, L. japonica; MRF, M. alba; MTH, M. canadensis; NPH, Nepeta tenuifolia; OPR, Ophiopogon japonicus; PCR, P. grandiflorus; PLF, P. frutescens; PMR, P. australis; PQR, P. quinquefolius; SCR, S. cusia; SKE, S. divaricata; STR, S. baicalensis; TSF, Trichosanthes kirilowii; ZGB, Z. officinale.
4 Discussion
TCM pharmacies existed even before the introduction of Western medicine in Taiwan. Over generations, they have accumulated countless folk formulae and TCM knowledge. These formulae were practiced during early medical deprivation in Taiwan, serving as pioneers of evidence-based medicine. This highlights that TCM pharmacies have become a vital repository for the ethnobotanical knowledge in Taiwan. However, as the older generation of owners ages and the younger generation is reluctant to take over, this valuable ethnobotanical knowledge is gradually disappearing. Therefore, documenting and preserving the folk formulae and TCM selection strategies accumulated by these pharmacies has become a key issue in the preservation of ethnobotanical knowledge in Taiwan.
The rapid global spread of the COVID-19 pandemic and the slow pace of new drug development have made the repurposing of existing medications, along with the use of Chinese herbal medicine and folk formulae, a feasible alternative solution (Fan et al., 2020). In this study, the most widely distributed plant families among the 70 medicinal materials were Lamiaceae, Apiaceae, and Fabaceae. Previous studies have mentioned that compounds such as terpenes, phenylpropanoids, and alkaloids can inhibit viral spike proteins, thus combating coronavirus infections (Babaeekhou et al., 2021; Boozari and Hosseinzadeh, 2021; Ma et al., 2021; Wang et al., 2022; Yi et al., 2022). These three plant families are rich in various terpenes, phenylpropanoids, and alkaloids, which may provide multi-target inhibition of viral infections (Kulkarni et al., 2020; Boozari and Hosseinzadeh, 2021; Liana and Phanumartwiwath, 2022). Furthermore, due to the uneven distribution of effective compounds within the plant, the choice of part used varies (Masumbu et al., 2023). In this study, the majority of the 70 medicinal materials belong to the radix and rhizoma. While the radix and rhizoma may contain the highest concentration of active compounds, harvesting them often results in the death of the plant, which is not in line with the United Nations’ Sustainable Development Goal—Life on Land (Department of Economic and Social Affairs, 2025). Therefore, future research should focus on studying the distribution of effective compounds within plants to identify alternative part used that can support sustainable resource development.
According to previous studies, common clinical manifestations of COVID-19 include fever, cough, systemic inflammatory and sputum production (An et al., 2021). The treatment strategy for COVID-19 in TCM focuses on expelling pathogenic factors and strengthening the body’s vitality (Wang et al., 2020). The former refers to eliminating pathogens and the inflammation they cause, often using heat-clearing and exterior-dispersing medicinal materials; the latter aims to enhance immunity, prevent and treat pathogen invasion, commonly through tonifying medicinal materials. In this study, the 70 medicinal materials are primarily characterized by bitter-cold, pungent-warm, and sweet-cold properties, with traditional uses focused on Qi-tonifying, heat clearing and detoxifying, and dispersing exterior pathogens. According to previous research, sweet-tasting medicinal materials are often rich in glycosides and amino acids, which mainly function to clear heat and tonify. Bitter-cold medicinal materials typically contain alkaloids and primarily serve to clear heat, with significant anti-inflammatory effects. Pungent-tasting medicinal materials contain terpenes and are known for their exterior-dispersing properties (Tie-jun and Liu, 2015; Wang et al., 2018). Other studies have found that bitter-cold medicinal materials can exert anti-inflammatory and angiogenic effects by inhibiting the NF-κB pathway and regulating IL1B, VEGF, and TNF (Zhang et al., 2013). The glycoside components found in sweet-tasting medicinal materials have shown immune-modulating effects in modern studies (Zhang Jing-ya et al., 2016). In summary, the selection of bitter-cold, pungent, and sweet medicinal materials by TCM pharmacies for anti-inflammatory and immune-regulating purposes is a rational combination for combating COVID-19.
The Louvain community detection model uses modularity to partition network nodes into communities with high internal cohesion and low external connections. It employs a hierarchical clustering method to gradually merge nodes, improving accuracy and efficiency (Traag et al., 2019). In this study, medicinal materials with an RFC greater than 0.05 were defined as commonly used medicinal materials. Each commonly used medicinal material represents one node, the number of positive Phi coefficient between any two medicinal materials is created as edges, and the Phi coefficient value is defined as edge weight in the Louvain community detection model. During the calculation, nodes were aggregated into communities to identify common medicinal material combinations used in TCM pharmacies for combating COVID-19. The results of this study indicate that the medicinal material combinations used in TCM pharmacies for combating COVID-19 can be categorized into four groups: Group A-D. Group A consists of 9 medicinal materials, corresponding to the formula NRICM101 (Figure 5) [Composition: G. uralensis (7.5 g), H. cordata (18.75 g), M. canadensis (11.25 g), M. alba (11.25 g), S. divaricata (7.5 g), N. tenuifolia (11.25 g), S. baicalensis (11.25 g), T. kirilowii (18.75 g), I. tinctoria (18.75 g), and Magnolia officinalis (11.25 g)]. Previous research has shown that NRICM101 has multi-target effects such as inhibiting the coronavirus spike protein, counteracting immune storms, and blocking viral replication, confirmed by assays such as the inhibition of 3CL protease, SARS-CoV-2 infection, and cytokine inhibition (Tsai et al., 2021). In addition, some studies have shown that NRICM101 shortened the hospitalization duration, reduced the duration of COVID-19 positive status, and decreased the number of days on mechanical ventilation in initially severe cases (Tsai et al., 2021; Chang et al., 2024). This study found that TCM pharmacies tend to use lower average dosages of each medicinal material compared to NRICM101. A possible reason is that the Group A contains many cold property medicinal materials (H. cordata, M. canadensis, M. alba, S. baicalensis, T. kirilowii, and S. cusia). Previous studies have suggested that NRICM101 may significantly increase the incidence of diarrhea (Chang et al., 2024), and excessive use of cold property medicinal materials can lead to cold-related symptoms such as diarrhea, cold limbs, and loss of appetite (Liu J. et al., 2020). Therefore, it is hypothesized that TCM pharmacies may reduce the dosage to minimize the occurrence of these side effects. Group B consists of 8 medicinal materials, with four herbs categorized as heat-clearing and exterior-releasing agents (L. japonica, C. cassia, Z. officinale, and I. tinctoria), and two herbs classified as tonifying agents (A. mongholicus and A. macrocephala). The selection of these medicinal materials aligns with TCM treatment strategies for COVID-19 (Wang et al., 2020). Previous studies have indicated that L. japonica, I. tinctoria, and A. mongholicus can inhibit M protein and spike protein on SARS-CoV-2, preventing viral entry into cells and replication (Mandal et al., 2021; Yeh et al., 2021). Meanwhile, C. cassia, Z. officinale, A. rugosa, and C. reticulata are rich in volatile compounds such as terpenes and phenolic compounds, which have been confirmed to possess antiviral activity in various studies (Astani et al., 2010; Wink, 2020; Elsebai and Albalawi, 2022). In addition, some studies have shown that Z. officinale can accelerate clinical recovery in mild and moderate COVID-19 cases and reduce pulmonary infiltrates (Singh et al., 2023; Ameri et al., 2024). Moreover, when considering the average dosages of the 8 medicinal materials in Group B, it was found that the dosage of C. cassia is higher than the standard dosage specified in the Taiwan Herbal Pharmacopeia fourth Edition, while the dosage of I. tinctoria is lower than the standard dosage (Taiwan Herbal Pharmacopeia 4th Edition Committee, 2021). Group C consists of five medicinal materials, all of which are symptomatic treatments. Medicinal materials such as O. japonicus, P. grandiflorus, P. frutescens, and C. morifolium are known for their antitussive, expectorant, and antipyretic effects (Zhang et al., 2015; Chen et al., 2016; Ahmed, 2018; Liu et al., 2024). Phragmites australis has been clinically proven to shorten the duration of fever in patients (Fang et al., 2024). In addition, previous study has shown that P. frutescens extract not only inhibits SARS-CoV-2 replication but also exhibits a synergistic effect when used in combination with remdesivir which is a Western medicine used to treat COVID-19 (Tang et al., 2021). Moreover, the average dosage of these five medicinal materials in Group C revealed that the dosage of P. australis is lower than the standard dosage specified in the Taiwan Herbal Pharmacopeia fourth Edition. Group D consists of 8 medicinal materials, 7 of which are tonifying herbs (Z. jujuba, L. chinense, H. polybotrys, C. pilosula, A. sinensis, P. quinquefolius, and P. ginseng). Previous research has highlighted the significant role of tonifying medicinal materials in the COVID-19 pandemic, as they regulate immunity, helping to prevent immune storms that could harm the body, while also boosting immune function to enhance the body’s ability to fight viral infections (Sun et al., 2003; Yang et al., 2022). In addition, one study has shown that taking P. ginseng can enhance and maintain the effectiveness of COVID-19 vaccines, with particularly significant effects observed in individuals over the age of 50 (Yoon et al., 2023). Moreover, among the 8 medicinal materials in Group D, the dosage of L. chinense is higher than the standard dosage specified in the Taiwan Herbal Pharmacopeia fourth Edition. Furthermore, several of the 30 commonly used medicinal materials identified in this study have been reported to contain bioactive compounds with validated anti-COVID-19 activity. Notable examples include licoricesaponin A3 and glycyrrhetinic acid from G. uralensis; kuwanon C and mulberrofuran G from M. alba; quercetin and luteolin from L. japonica and P. frutescens; platycodin D from P. grandiflorus; baicalin and baicalein from S. baicalensis; ginsenoside compound K from P. ginseng; and obacunone, limonin, and nomilin from C. reticulata (Song et al., 2020; Kim et al., 2021; Liu et al., 2021; Magurano et al., 2021; Dissook et al., 2022; Kim et al., 2022a; Kim et al., 2022b; Yi et al., 2022; Boopathi et al., 2023; Gao et al., 2023). These compounds are primarily classified as terpenoids or polyphenols, indicating that future phytochemical screening for anti-COVID-19 candidates may be most fruitful when focused on these two classes of natural products.
Figure 5. Photograph of NRICM101 medicinal material composition.
In summary, the medicinal material combinations used in TCM pharmacies to combat COVID-19 can be categorized into four groups. Group A consists mainly of heat-clearing herbs, which are more suitable for moderate to severe COVID-19 patients to combat persistent high fever and inflammatory responses caused by viral infections. Group B is a mix of heat-clearing and tonifying herbs, making it suitable for mild COVID-19 patients as it combats the systemic inflammatory and boosts immunity simultaneously. Group C includes symptomatic treatments, which are appropriate for patients experiencing related symptoms such as cough and sputum production, or as an adjunct treatment in Group A and Group B therapies. Group D consists mainly of tonifying herbs, making it suitable for the public who have not yet contracted COVID-19, serving as an immunity-boosting regimen. Additionally, the dosages of the 30 commonly used medicinal materials vary across different pharmacies, and some of the average dosages do not conform to the standard dosages outlined in the Taiwan Herbal Pharmacopeia fourth Edition. This phenomenon reflects the unique approach TCM pharmacies take in selecting medicinal material dosages.
This study has several limitations. Firstly, the research is based on previous studies and makes pharmacological inferences regarding the commonly used anti-COVID-19 medicinal materials in TCM pharmacies. However, from a formulaic perspective, while the efficacy of Group A has been validated by research, Groups B-D still lack sufficient experimental evidence to support the effectiveness and safety of their formulae. Secondly, the doses of medicinal materials such as C. cassia, I. tinctoria, P. australis, and L. chinense mentioned in this study do not conform to the standard dosages outlined in the Taiwan Herbal Pharmacopeia fourth Edition, and thus their safety requires further research.
Despite these limitations, the results of this study not only provide numerous candidate medicinal materials and formulae for future anti-coronavirus treatments, but also contribute to the documentation of the ethnobotanical knowledge in combating COVID-19 from TCM pharmacy in Taiwan, thus supporting the achievement of the United Nations Sustainable Development Goals.
5 Conclusion
This study is the first ethnobotanical research on folk formulae for Anti-COVID-19 in Taiwan. It consolidates the use of 70 medicinal materials selected by TCM pharmacies for the prevention and treatment of COVID-19, with 30 commonly used medicinal materials categorized into four distinct formula groups, each targeting different stages of the disease. More importantly, this study employs an ethnobotanical research approach to not only identify potential herbs and formulae for combating COVID-19 but also to document and digitize traditional knowledge, ensuring its preservation in line with the United Nations Sustainable Development Goals. In the future., a “disease course-oriented specialized prescription model” will be adapted with reference to international literature and the development of COVID-19 symptoms reported by NIH. Different combinations of medicinal materials will be formulated in response to the rapid development of the disease, providing the clinical outcome with a reference for the selection of prescriptions for different stages of the disease.
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
Ethics statement
The studies involving humans were approved by Research Ethics Committee China Medical University and Hospital, Taichung, Taiwan. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because Non-interventional studies (e.g., observational studies of behavior or nutrition).
Author contributions
M-HC: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Project administration, Software, Visualization, Writing – original draft, Writing – review and editing. C-YK: Conceptualization, Investigation, Methodology, Project administration, Writing – original draft, Writing – review and editing. T-WC: Conceptualization, Investigation, Software, Visualization, Writing – review and editing. C-RH: Conceptualization, Investigation, Writing – review and editing. J-GL: Conceptualization, Investigation, Methodology, Project administration, Writing – review and editing. JC: Conceptualization, Investigation, Supervision, Validation, Writing – review and editing. S-SH: Conceptualization, Investigation, Methodology, Supervision, Validation, Writing – review and editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. This research was funded by the Tsuzuki Institute for Traditional Medicine, Grant numbers 108727B8, 109727B8 and 110727B8; China Medical University, Grant numbers CMU108-MF-116, CMU108-SR-101, CMU108-N-22, CMU109-MF-95, CMU109-MF-109 and CMU111-MF-75; the Ministry of Science and Technology, Grant number MOST 107-2320-B-039-030-MY3, 109-2320-B-039-026, 109-2813-C-039-061-B and 110-2320-B-039-021. The China Medical University under the Higher Education Sprout Project and Teaching Practice Research Program, Grant number 1077170A, of the Ministry of Education of Taiwan.
Acknowledgments
The authors thank the herbarium of China Medical University for providing us with space to store the medicinal materials for this study. Also, we would like to thank the 64th and 61st pharmacy students of China Medical University for their assistance in this study. Finally, we sincerely appreciate Shengda TCM pharmacy for providing us with a location for photography.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2025.1586334/full#supplementary-material
References
Ahmad, K. S., Hamid, A., Nawaz, F., Hameed, M., Ahmad, F., Deng, J., et al. (2017). Ethnopharmacological studies of indigenous plants in Kel village, Neelum Valley, Azad Kashmir, Pakistan. J. Ethnobiol. Ethnomed 13 (1), 68. doi:10.1186/s13002-017-0196-1
Ahmed, H. M. (2018). Ethnomedicinal, phytochemical and pharmacological investigations of Perilla frutescens (L.) britt. Molecules 24 (1), 102. doi:10.3390/molecules24010102
Ahn, D. G., Shin, H. J., Kim, M. H., Lee, S., Kim, H. S., Myoung, J., et al. (2020). Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J. Microbiol. Biotechnol. 30 (3), 313–324. doi:10.4014/jmb.2003.03011
Ameri, A., Farashahinejad, M., Davoodian, P., Safa, O., Hassaniazad, M., Parsaii, M., et al. (2024). The efficacy and safety of ginger (Zingiber officinale) rhizome extract in outpatients with COVID-19: a randomized double-blind placebo-control clinical trial. Med. Baltim. 103 (22), e38289. doi:10.1097/md.0000000000038289
An, X., Duan, L., Zhang, Y. H., Jin, D., Zhao, S., Zhou, R. R., et al. (2021). The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19. Chin. Med. 16 (1), 44. doi:10.1186/s13020-021-00454-x
Asselah, T., Durantel, D., Pasmant, E., Lau, G., and Schinazi, R. F. (2021). COVID-19: discovery, diagnostics and drug development. J. Hepatol. 74 (1), 168–184. doi:10.1016/j.jhep.2020.09.031
Astani, A., Reichling, J., and Schnitzler, P. (2010). Comparative study on the antiviral activity of selected monoterpenes derived from essential oils. Phytother. Res. 24 (5), 673–679. doi:10.1002/ptr.2955
Babaeekhou, L., Ghane, M., and Abbas-Mohammadi, M. (2021). In silico targeting SARS-CoV-2 spike protein and main protease by biochemical compounds. Biol. Bratisl. 76 (11), 3547–3565. doi:10.1007/s11756-021-00881-z
Boopathi, V., Nahar, J., Murugesan, M., Subramaniyam, S., Kong, B. M., Choi, S. K., et al. (2023). In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K. Heliyon 9 (9), e19341. doi:10.1016/j.heliyon.2023.e19341
Boozari, M., and Hosseinzadeh, H. (2021). Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytother. Res. 35 (2), 864–876. doi:10.1002/ptr.6873
Chang, W. K., Wang, C. J., Tsai, T. H., Sun, F. J., Chen, C. H., Kuo, K. C., et al. (2024). The clinical application of traditional Chinese medicine NRICM101 in hospitalized patients with COVID-19. Expert Rev. Anti Infect. Ther. 22 (7), 587–595. doi:10.1080/14787210.2024.2313054
Chen, M. H., Chen, X. J., Wang, M., Lin, L. G., and Wang, Y. T. (2016). Ophiopogon japonicus--A phytochemical, ethnomedicinal and pharmacological review. J. Ethnopharmacol. 181, 193–213. doi:10.1016/j.jep.2016.01.037
Chinese Pharmacopoeia Commission (2020). Pharmacopoeia of People’s Republic of China. Beijing, China: China Medical Science Press.
Chytrý, M., Tichý, L., Holt, J., and Botta-Dukát, Z. (2002). Determination of diagnostic species with statistical fidelity measures. J. Veg. Sci. 13 (1), 79–90. doi:10.1658/1100-9233(2002)013[0079:dodsws]2.0.co;2
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5 (4), 536–544. doi:10.1038/s41564-020-0695-z
COVID-19 Treatment Guidelines Panel (2024). Coronavirus disease 2019 (COVID-19) treatment guidelines. State of Maryland, United States: N.I.o. Health.
Cui, Y., Wang, S., and Yan, S. (2016). Evaluating the applicability of Phi coefficient in indicating habitat preferences of Forest soil fauna based on a single field Study in subtropical China. PLoS One 11 (3), e0150380. doi:10.1371/journal.pone.0150380
Del Vecchio, L., Balafa, O., Dounousi, E., Ekart, R., Fernandez, B. F., Mark, P. B., et al. (2024). COVID-19 and cardiovascular disease in patients with chronic kidney disease. Nephrol. Dial. Transpl. 39 (2), 177–189. doi:10.1093/ndt/gfad170
Department of Chinese Medicine and Pharmacy (2024). Taiwan herbal Pharmacopeia database. Available online at: https://www.cmthp.mohw.gov.tw/English/index (Accessed July 29, 2024).
Department of Economic and Social Affairs (2025). Sustainable development: the 17 goals. Available online at: https://sdgs.un.org/goals ([Accessed Febrary 21, 2025).
Dissook, S., Umsumarng, S., Mapoung, S., Semmarath, W., Arjsri, P., Srisawad, K., et al. (2022). Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of JAK1/STAT3 pathway: a potential anti-inflammatory compound against inflammation-induced long-COVID. Front. Med. (Lausanne) 9, 1072056. doi:10.3389/fmed.2022.1072056
Elsebai, M. F., and Albalawi, M. A. (2022). Essential oils and COVID-19. Molecules 27 (22), 7893. doi:10.3390/molecules27227893
Fan, A. Y., Gu, S., and Alemi, S. F.Research Group for Evidence-based Chinese Medicine (2020). Chinese herbal medicine for COVID-19: current evidence with systematic review and meta-analysis. J. Integr. Med. 18 (5), 385–394. doi:10.1016/j.joim.2020.07.008
Fang, M., Kong, L. Y., Ji, G. H., Pu, F. L., Su, Y. Z., Li, Y. F., et al. (2024). Chinese medicine Phragmites communis (Lu Gen) for acute respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. Front. Pharmacol. 15, 1242525. doi:10.3389/fphar.2024.1242525
Gao, B., Zhu, L., Liu, Z., Li, Y., He, X., Wu, X., et al. (2023). Chemical composition of honeysuckle (Lonicerae japonicae) extracts and their potential in inhibiting the SARS-CoV-2 spike protein and ACE2 binding, suppressing ACE2, and scavenging radicals. J. Agric. Food Chem. 71 (15), 6133–6143. doi:10.1021/acs.jafc.3c00584
Hu, F. P., Liao, C. C., Chen, T. L., Yeh, C. C., Shi, L., and Shih, C. C. (2020). Prevalence, expenditures, and associated factors of purchasing non-prescribed Chinese herbal medicine in Taiwan. PLoS One 15 (10), e0240311. doi:10.1371/journal.pone.0240311
Kim, T. Y., Jeon, S., Jang, Y., Gotina, L., Won, J., Ju, Y. H., et al. (2021). Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion. Exp. Mol. Med. 53 (5), 956–972. doi:10.1038/s12276-021-00624-9
Kim, Y. S., Kim, B., Kwon, E. B., Chung, H. S., and Choi, J. G. (2022a). Mulberrofuran G, a mulberry component, prevents SARS-CoV-2 infection by blocking the interaction between SARS-CoV-2 spike protein S1 receptor-binding domain and human angiotensin-converting enzyme 2 receptor. Nutrients 14 (19), 4170. doi:10.3390/nu14194170
Kim, Y. S., Kwon, E. B., Kim, B., Chung, H. S., Choi, G., Kim, Y. H., et al. (2022b). Mulberry component kuwanon C exerts potent therapeutic efficacy in vitro against COVID-19 by blocking the SARS-CoV-2 spike S1 RBD:ACE2 receptor interaction. Int. J. Mol. Sci. 23 (20), 12516. doi:10.3390/ijms232012516
Kulkarni, S. A., Nagarajan, S. K., Ramesh, V., Palaniyandi, V., Selvam, S. P., and Madhavan, T. (2020). Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein. J. Mol. Struct. 1221, 128823. doi:10.1016/j.molstruc.2020.128823
Liana, D., and Phanumartwiwath, A. (2022). Leveraging knowledge of Asian herbal medicine and its active compounds as COVID-19 treatment and prevention. J. Nat. Med. 76 (1), 20–37. doi:10.1007/s11418-021-01575-1
Liu, H., Ye, F., Sun, Q., Liang, H., Li, C., Li, S., et al. (2021). Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro. J. Enzyme Inhib. Med. Chem. 36 (1), 497–503. doi:10.1080/14756366.2021.1873977
Liu, J., Feng, W., and Peng, C. (2020a). A Song of ice and fire: cold and hot properties of traditional Chinese medicines. Front. Pharmacol. 11, 598744. doi:10.3389/fphar.2020.598744
Liu, M., Gao, Y., Yuan, Y., Yang, K., Shi, S., Zhang, J., et al. (2020b). Efficacy and safety of integrated traditional Chinese and Western Medicine for Corona Virus disease 2019 (COVID-19): a systematic review and meta-analysis. Pharmacol. Res. 158, 104896. doi:10.1016/j.phrs.2020.104896
Liu, Y., Lu, C., Zhou, J., Zhou, F., Gui, A., Chu, H., et al. (2024). Chrysanthemum morifolium as a traditional herb: a review of historical development, classification, phytochemistry, pharmacology and application. J. Ethnopharmacol. 330, 118198. doi:10.1016/j.jep.2024.118198
Ma, L. L., Liu, H. M., Liu, X. M., Yuan, X. Y., Xu, C., Wang, F., et al. (2021). Screening S protein - ACE2 blockers from natural products: strategies and advances in the discovery of potential inhibitors of COVID-19. Eur. J. Med. Chem. 226, 113857. doi:10.1016/j.ejmech.2021.113857
Magurano, F., Sucameli, M., Picone, P., Micucci, M., Baggieri, M., Marchi, A., et al. (2021). Antioxidant activity of citrus limonoids and investigation of their virucidal potential against SARS-CoV-2 in cellular models. Antioxidants (Basel) 10 (11), 1794. doi:10.3390/antiox10111794
Mandal, A., Jha, A. K., and Hazra, B. (2021). Plant products as inhibitors of coronavirus 3CL protease. Front. Pharmacol. 12, 583387. doi:10.3389/fphar.2021.583387
Marzolini, C., Kuritzkes, D. R., Marra, F., Boyle, A., Gibbons, S., Flexner, C., et al. (2022). Recommendations for the management of drug-drug interactions between the COVID-19 antiviral Nirmatrelvir/Ritonavir (Paxlovid) and comedications. Clin. Pharmacol. Ther. 112 (6), 1191–1200. doi:10.1002/cpt.2646
Masumbu, F. F. F., Mwamatope, B., Tembo, D., Mwakikunga, A., and Kamanula, J. (2023). Ethnobotanical survey of medicinal plants claimed by traditional herbal practitioners to manage cancers in Malawi. J. Herb. Med. 42, 100796. doi:10.1016/j.hermed.2023.100796
Ministry of Health and Welfare (2024). The administration of pharmaceutical affairs. Taipei, Taiwan: D. o. Statistics.
National Administration of Traditional Chinese Medicine “Chinese Materia Medica” Editorial Board (1999). Chinese Materia medica. Shanghai: Scientific and Technical Publishers.
Royal Botanic Gardens, K., and Garden, M. B. (2024). World flora online. Available online at: http://www.worldfloraonline.org/(Accessed July 02, 2024).
Shi, N., Liu, B., Liang, N., Ma, Y., Ge, Y., Yi, H., et al. (2020). Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: a retrospective multicenter cohort study. Pharmacol. Res. 161, 105290. doi:10.1016/j.phrs.2020.105290
Singh, H., Yadav, B., Rai, A. K., Srivastava, S., Saiprasad, A., Jameela, S., et al. (2023). Ashwagandha (Withania somnifera) and Shunthi (Zingiber officinale) in mild and moderate COVID-19: an open-label randomized controlled exploratory trial. Complement. Ther. Med. 76, 102966. doi:10.1016/j.ctim.2023.102966
Singh, T. U., Parida, S., Lingaraju, M. C., Kesavan, M., Kumar, D., and Singh, R. K. (2020). Drug repurposing approach to fight COVID-19. Pharmacol. Rep. 72 (6), 1479–1508. doi:10.1007/s43440-020-00155-6
Song, J. W., Long, J. Y., Xie, L., Zhang, L. L., Xie, Q. X., Chen, H. J., et al. (2020). Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi. and its probably potential therapeutic effects on COVID-19: a review. Chin. Med. 15, 102. doi:10.1186/s13020-020-00384-0
Sun, A., Chia, J. S., Chang, Y. F., and Chiang, C. P. (2003). Levamisole and Chinese medicinal herbs can modulate the serum interleukin-6 level in patients with recurrent aphthous ulcerations. J. Oral Pathol. Med. 32 (4), 206–214. doi:10.1034/j.1600-0714.2003.00096.x
Taiwan Herbal Pharmacopeia 4th Edition Committee (2021). Taiwan herbal pharmacopeia. 4th Edition. Taipei, Taiwan: Department of Chinese Medicine and Pharmacy, Ministry of Health and Welfare.
Tang, W. F., Tsai, H. P., Chang, Y. H., Chang, T. Y., Hsieh, C. F., Lin, C. Y., et al. (2021). Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation. Biomed. J. 44 (3), 293–303. doi:10.1016/j.bj.2021.01.005
Tie-jun, Z., and Chang-xiao, L. (2015). Identification of Chinese materia medica and its chemical biology characterization path on five taste theory. Chin. Traditional Herb. Drugs 46 (1), 1–6. doi:10.7501/j.issn.0253-2670.2015.01.001
Traag, V. A., Waltman, L., and van Eck, N. J. (2019). From Louvain to Leiden: guaranteeing well-connected communities. Sci. Rep. 9 (1), 5233. doi:10.1038/s41598-019-41695-z
Tsai, K. C., Huang, Y. C., Liaw, C. C., Tsai, C. I., Chiou, C. T., Lin, C. J., et al. (2021). A traditional Chinese medicine formula NRICM101 to target COVID-19 through multiple pathways: a bedside-to-bench study. Biomed. Pharmacother. 133, 111037. doi:10.1016/j.biopha.2020.111037
Wang, C., Ming, H., Jia, W., Su, W., Zhan, L. R., Luo, D., et al. (2020). Analysis of medication regularity and pharmacodynamic characteristics of traditional Chinese medicine treatment in 444 severe cases of COVID-19. Zhongguo Zhong Yao Za Zhi 45 (13), 3007–3012. doi:10.19540/j.cnki.cjcmm.20200427.501
Wang, W. J., Chen, Y., Su, W. C., Liu, Y. Y., Shen, W. J., Chang, W. C., et al. (2022). Peimine inhibits variants of SARS-CoV-2 cell entry via blocking the interaction between viral spike protein and ACE2. J. Food Biochem. 46 (10), e14354. doi:10.1111/jfbc.14354
Wang, Z., Xia, Q., Liu, X., Liu, W., Huang, W., Mei, X., et al. (2018). Phytochemistry, pharmacology, quality control and future research of Forsythia suspensa (Thunb.) vahl: a review. J. Ethnopharmacol. 210, 318–339. doi:10.1016/j.jep.2017.08.040
Wink, M. (2020). Potential of DNA intercalating alkaloids and other plant secondary metabolites against SARS-CoV-2 causing COVID-19. Diversity 12 (5), 175. doi:10.3390/d12050175
World Health Organization (2024). WHO COVID-19 dashboard. Available online at: https://data.who.int/dashboards/covid19/cases (Accessed 28May, 2024).
Xian-Zhe, Z. (2007). Color Atlas for the authentic and superior Chinese material medica. Taichung, Taiwan: China Medical University.
Yang, F., Zhang, X., Zhang, Z., Lu, H., Li, J., Bai, N., et al. (2022). Efficacy and safety of Qi and blood tonic Chinese medicines in the treatment of COVID-19: a protocol for systematic review and meta-analysis. Med. Baltim. 101 (49), e32136. doi:10.1097/md.0000000000032136
Yeh, Y. C., Doan, L. H., Huang, Z. Y., Chu, L. W., Shi, T. H., Lee, Y. R., et al. (2021). Honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) suppress SARS-CoV-2 entry and COVID-19 related cytokine storm in vitro. Front. Pharmacol. 12, 765553. doi:10.3389/fphar.2021.765553
Yi, Y., Li, J., Lai, X., Zhang, M., Kuang, Y., Bao, Y. O., et al. (2022). Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection. J. Adv. Res. 36, 201–210. doi:10.1016/j.jare.2021.11.012
Yoon, J., Park, B., Kim, H., Choi, S., and Jung, D. (2023). Korean red ginseng potentially improves maintaining antibodies after COVID-19 vaccination: a 24-week longitudinal study. Nutrients 15 (7), 1584. doi:10.3390/nu15071584
Yousefi, H., Mashouri, L., Okpechi, S. C., Alahari, N., and Alahari, S. K. (2021). Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: a review describing drug mechanisms of action. Biochem. Pharmacol. 183, 114296. doi:10.1016/j.bcp.2020.114296
Zhang, B., Wang, X., and Li, S. (2013). An integrative platform of TCM network pharmacology and its application on a herbal formula, qing-luo-yin. Evid. Based Complement. Altern. Med. 2013, 456747. doi:10.1155/2013/456747
Zhang, L., Wang, Y., Yang, D., Zhang, C., Zhang, N., Li, M., et al. (2015). Platycodon grandiflorus - an ethnopharmacological, phytochemical and pharmacological review. J. Ethnopharmacol. 164, 147–161. doi:10.1016/j.jep.2015.01.052
Zhang Jing-ya, C. H., Su-xiao, G., Jun, X., Yan-qi, H., Tie-jun, Z., and Chang-xiao, L. (2016). Expression of sweet-taste of Chinese materia medica and its application in clinical compatibility. Chin. Traditional Herb. Drugs 47 (4), 533–539. doi:10.7501/j.issn.0253-2670.2016.04.001
Zhao, Z., Liang, Z., and Ping, G. (2011). Macroscopic identification of Chinese medicinal materials: traditional experiences and modern understanding. J. Ethnopharmacol. 134 (3), 556–564. doi:10.1016/j.jep.2011.01.018
Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., et al. (2020a). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579 (7798), 270–273. doi:10.1038/s41586-020-2012-7
Zhou, Y., Wang, F., Tang, J., Nussinov, R., and Cheng, F. (2020b). Artificial intelligence in COVID-19 drug repurposing. Lancet Digit. Health 2 (12), e667–e676. doi:10.1016/s2589-7500(20)30192-8
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., et al. (2020). A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382 (8), 727–733. doi:10.1056/NEJMoa2001017
Glossary
ADR Angelica dahurica (Hoffm.) Benth. and Hook.f. ex Franch. and Sav.
AFI Citrus × aurantium L.
AGR Astragalus mongholicus Bunge
ALI Alisma plantago-aquatica subsp. orientale (Sam.) Sam.
AMR Atractylodes macrocephala Koidz.
ARE Aster tataricus L.f.
ARR Asarum heterotropoides F.Schmidt
ASA Prunus sibirica L.
ASE Eleutherococcus senticosus (Rupr. and Maxim.) Maxim.
ASR Angelica sinensis (Oliv.) Diels
ATH Agastache rugosa (Fisch. and C.A.Mey.) Kuntze
BPR Bupleurum chinense DC.
BTR Bletilla striata (Thunb.) Rchb.f.
CLR Curcuma longa L.
CMC Cinnamomum cassia (L.) J.Presl (Cortex)
CMR Cinnamomum cassia (L.) J.Presl (Ramulus)
COVID-19 Coronavirus Disease 2019
CRP Citrus reticulata Blanco
CSF Chrysanthemum morifolium Ramat.
CSR Codonopsis pilosula (Franch.) Nannf.
CXR Ligusticum striatum DC.
DSR Dioscorea oppositifolia L.
EBF Eriobotrya japonica (Thunb.) Lindl.
EDH Ephedra sinica Stapf
EMC Eucommia ulmoides Oliv.
FSR Forsythia suspensa (Thunb.) Vahl
FTB Fritillaria thunbergii Miq.
GLY Glycyrrhiza uralensis Fisch.
GNR Glehnia littoralis F.Schmidt ex Miq.
GSG Panax ginseng C.A.Mey.
HCE Helminthostachys zeylanica (L.) Hook.
HDR Hedysarum polybotrys Hand.-Mazz.
HNH Houttuynia cordata Thunb.
IPR Imperata cylindrica (L.) Raeusch.
ISR Iris domestica (L.) Goldblatt and Mabb.
ITR Isatis tinctoria L.
JJB Ziziphus jujuba Mill.
LBS Lilium lancifolium Thunb.
LCF Lycium chinense Mill.
LJF Lonicera japonica Thunb.
LOP Lophatherum gracile Brongn
LPH Lycopus lucidus var. hirtus Regel
MNC Magnolia officinalis Rehder and E.H.Wilson
MOHW the Ministry of Health and Welfare
MRC Morus alba L. (Cortex)
MRF Morus alba L. (Folium)
MTH Mentha canadensis L.
NBF Nelumbo nucifera Gaertn.
NIH National Institutes of Health
NPH Nepeta tenuifolia Benth.
OPR Ophiopogon japonicus (Thunb.) Ker Gawl.
PCR Platycodon grandiflorus (Jacq.) A.DC.
PLC Perilla frutescens (L.) Britton (Caulis)
PLF Perilla frutescens (L.) Britton (Folium)
PLR Pinellia ternata (Thunb.) Makino
PMR Phragmites australis (Cav.) Trin. ex Steud.
POR Poria cocos (Schwein.) F.A. Wolf
PQR Panax quinquefolius L.
PRA Paeonia lactiflora Pall.
PRR Pueraria montana var. chinensis (Ohwi) Sanjappa and Pradeep
QFPDD Qingfei Paidu Decoction
RFC Relative frequency of citation
RMR Reynoutria multiflora (Thunb.) Moldenke
RNR Rehmannia glutinosa (Gaertn.) DC.
SCR Strobilanthes cusia (Nees) Kuntze
SKE Saposhnikovia divaricata (Turcz.) Schischk.
SME Salvia miltiorrhiza Bunge
SNR Stemona sessilifolia (Miq.) Miq.
SPR Scrophularia ningpoensis Hemsl.
SPS Scaphium affine (Mast.) Pierre
STF Siraitia grosvenorii (Swingle) C.Jeffrey ex A.M.Lu and Zhi.Y.Zhang
STR Scutellaria baicalensis Georgi
TCM traditional Chinese medicine
TSF Trichosanthes kirilowii Maxim.
TWD97 the Taiwan Geodetic Datum 1997
TXH Taraxacum mongolicum Hand.-Mazz.
WHO World Health Organization
ZGB Zingiber officinale Roscoe
Keywords: SARS-CoV-2, COVID-19, traditional Chinese medicine, ethnobotany, Taiwan
Citation: Chi M-H, Ko C-Y, Chi T-W, Huang C-R, Lin J-G, Chao J and Huang S-S (2025) Ethnobotanical survey of herbal medicines for anti-COVID-19 used by traditional Chinese medicine pharmacies in Taiwan. Front. Pharmacol. 16:1586334. doi: 10.3389/fphar.2025.1586334
Received: 02 March 2025; Accepted: 18 July 2025;
Published: 03 September 2025.
Edited by:
Dâmaris Silveira, University of Brasilia, BrazilReviewed by:
Chandrabose Selvaraj, Amet University, IndiaOmar Estrada, Instituto Venezolano de Investigaciones Científicas (IVIC), Venezuela
Kameswara Rao Badri, Morehouse School of Medicine, United States
Copyright © 2025 Chi, Ko, Chi, Huang, Lin, Chao and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Shyh-Shyun Huang, c3NodWFuZ0BtYWlsLmNtdS5lZHUudHc=; Jung Chao, anVuZ2NoYW9AbWFpbC5jbXUuZWR1LnR3
†These authors have contributed equally to this work and share first authorship