Geographic Information Database of Herbs against COVID-19 in Thailand: The Medicinal Plants those Folk Healers Commonly Used for Treatment and Boosting People's Immunity

Chaimongkhon, K.,^1,2 Kijphati, R.,^3, Krates, J.,^3,4 Sirisa-ad, P.,⁵ Junto, E.,⁶ Aneksak, W.,^1,2 Scully, P.,⁷Amornmahaphun, S.,³ Pholputta, L.,¹ Buadang, S.,⁴ Noradee, S.,⁴ Kanjaras, P.,⁴ Toemjai, T.,⁴Roongpisuthipong, A.,⁸ Viegus, Z.,¹ Sujayanont, P.¹ and Nithikathkul, C.^1*

¹Tropical Health Innovation Research Unit, Faculty of Medicine, Mahasarakham University, Thailand

E-mail: nithikethkul2016@gmail.com^*

²Ph.D in Health Science Program Faculty of Medicine, Mahasarakham University, Thailand

³Office of Permanent Secretary, Ministry of Public Health, Thailand

⁴ Office of public health research and innovation administration, Office of Permanent Secretary, Ministry of Public Health, Thailand

⁵ Faculty of Pharmacy, Chiang Mai University, Chiang Mai Thailand

⁶ Sirindhorn college of Public Health Phitsanulok, Faculty of Public Health and Allied Health Science, Praboromarajchanok Institute,Thailand

⁷ Faculty of Information Technology, Mahasarakham University, Thailand

⁸ Faculty of Allied Health Science, Suamsunandha Rajabhat University, Thailand

⁹ Office of Public Health Research and Innovation Administration, Office of Permanent Secretary, Ministry of Public Health, Thailand

¹⁰ Sirindhorn college of Public Health Ubon Ratchathani, Faculty of Public Health and Allied Health Science, Praboromarajchanok Institute, Thailand

¹¹ Srimahasarakham Nursing College, Faculty of Nursing, Praboromarajchanok Institute, Thailand

*Corresponding Author

Abstract

The rapid outbreak of coronavirus disease 2019 (COVID-19) has demonstrated the need for the development of new vaccine candidates and therapeutic drugs to fight against the underlying virus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Currently, no antiviral treatment is available to treat COVID-19, as treatment is mostly directed at relieving the symptoms, and retrospectively, herbal medicinal plants have been used for thousands of years as a medicinal alternative, including for the treatment of various viral illnesses. The aim of this study is to conduct a survey in terms of identifying the area where the population commonly uses the medicinal plant in comparison to the cumulative number of COVID-19 reports in each area, including the classification of medicinal plants by type and a stepwise approach shown in the form of geographic information maps in those areas. An observational study on the cultivation of medicinal plants those folk healers commonly used for healing. beneficial for treatment and strengthening the immunity of the people in 9 provinces of Thailand. According to the situation of the spread of COVID-19, there are people infected in Thailand. In each area where medicinal plants were used, there was a significant positive result when compared to the cumulative COVID-19 incidence; the majority was with the lowest cumulative COVID-19 incidence and the most commonly used medicinal plants, such as Artemisia annua, Harrisonia perforate (Blanco) Merr, Capparis micracantha, Tacca leontopetaloides, Andrographis paniculata, Phyllanthus emblica, Ficus carica, Tiliacora triandra, Terminalia bilaria, and Cannabis indica. This study exercise may lend enough credence to the potential value of Thai medicinal plants (herbs) as possible leads in anti-COVID-19 drug discovery through research and development.

Keywords: COVID-19, Herb, Medicinal Plant, Viral Infection and Thailand

Furthermore, the rapid outbreak of coronavirus disease 2019 (COVID-19) has demonstrated the need for the development of new vaccine candidates and therapeutic drugs to fight against the underlying virus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Currently, no antiviral treatment is available to treat COVID-19, as treatment is mostly directed at relieving the symptoms, and retrospectively, herbal medicinal plants have been used for thousands of years as a medicinal alternative, including for the treatment of various viral illnesses. However, a comprehensive description of the use of various medicinal plants in treating coronavirus infection has yet to be adequately described, particularly their modes of action.

During the spread of COVID-19 in Thailand, the cumulative COVID-19 incidence rate was mostly high in provinces with high population densities, including adjacent areas, and some provinces with high population densities that commonly used traditional medicinals had a low cumulative incidence rate. Therefore, researchers discovered that the medicinal plants commonly used by folk healers for healing are beneficial for treatment and boosting people's immunity. There was evidence that several medicinal plants were mostly used in nine provinces of Thailand, such as Chiang Rai, Chiang Mai, Lamphun, Phitsanulok, Nakhon Phanom, Maha Sarakham, Chaiyaphum, Nakhon Phanom, and Ubon Ratchatani, in comparison with the cumulative COVID-19 incidence reported in each area, respectively, in this survey result, showing that several medicinal plants for COVID-19 were mostly used in each province, there was:Artemisia annua, Harrisonia perforate (Blanco) Merr, Capparis micracantha, Tacca leontopetaloides, Andrographis paniculate, Phyllanthus emblica, Ficus carica, Tiliacora triandra, Terminalia chebula, Terminalia belliriaandCannabis indicain comparison with the cumulative COVID-19 incidence presented, there were mostly low incidence rates. This finding is in accordance with the preview studies [11] [12] [13] [14] [25] [31] and [32]. Therefore, the researchers assumed that those are strong candidate treatments, including transformation to modern medicine for further COVID-19 or other relevant viral pandemic treatments.

Artemisia annuaArtemisia annua was found in several locations throughout the study area and was one of the most commonly used traditional medicines in Thailand during the COVID-19 period; the survey results showed that in those areas where it was used, there was a low incidence rate when compared to the cumulative COVID-19 incidence in these areas. Artemisia annua has been used for the treatment of various diseases since ancient times, such as having been revealed to have inhibitory effects against parasites (e.g., Plasmodium spp, Toxoplasma gondii, Leishmania spp), viruses (e.g., hepatitis A virus, herpes simplex viruses 1 and 2, human immunodeficiency virus), and fungi (Candida, Malassezia, Saccharomyces spp) and bacteria (e.g., Enterococcus, Streptococcus, Staphylococcus, Bacillus, Listeria, Haemophilus, Escherichia, Pseudomonas, Klebsiella, Acinetobacter, Salmonella, and Yersinia spp.) [9]. However, recently, Artemisia annua, including other specie such as Artemisia afra, has been discovered to exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19-related symptoms and is one of the potential herbal extracts that play a role in viral attachment and penetration, viral RNA and protein synthesis inhibition, inhibition of viral key proteins such as 3-chymotrypsin-like cysteine protease (3CLpro) and papain-like protease 2 (PLpro), as well as other mechanisms such as viral release inhibition and enhanced host immunity, including anti-inflammatory effects [33] [35] and [36].

Harrisonia perforate (Blanco) Merr,a medicinal plant discovered in all areas of the survey, was one of the most commonly used medicinal plants for healing by folk healers during the COVID-19 pandemic.The survey resulted in a low rate of cumulative incidence when compared to the cumulative COVID-19 incidence in each area discovered with Harrisonia perforata as a medicinal plant. This is consistent with the findings of Phumthum's (2020) and Tang et al.'s (2021) studies, which identified Harrisonia perforate (Blanco) Merr as a medicinal plant species used to treat infection-related diseases [37] and [38] Therefore, this medicinal plant is necessary for advancement in development and represents a modern pharmaceutical novelty, particularly against viral infections with characteristics similar to those of COVID-19.

Andrographis paniculate,it was one of the commont folk healers used in Thailand to treat a several infection diseses thereby, and the survey result showed in this study evidentialy, the area where found this medicinal plant was presented low cumulative COVID-19 incidence this result in accordance with several studies showind that Andrographis paniculate (AP) (Kalmegh) were isolated the Bioactive Andrographolide (AGL; C20H30O5) is a diterpenoid lactones having multifunctional medicinal properties including anti-manic, anti-inflammatory, liver, and lung protective.

Andrographolide (AGL) is known for its immunostimulant activity against a variety of microbial infections thereby, regulating classical and alternative macrophage activation, Ag-specific antibody production during immune disorder therapy. therefore regarding the result in accordance the possible role of AGL as a promising herbal-chemo remedy during human diseases, viral infections and as an immunity booster [21] and [24].

Phyllanthus emblica, which is commonly used in Thailand, produced a significant result when compared to the COVID-19 cumulative incidence in each area studied; thus, according to Varnasseri et al., [39] study, organic herbal Phyllanthus emblica (Amla) tea may reduce symptom recovery times and length of stay (LOS) in hospital in COVID-19 patients, and it showed an ameliorative effect on the severity of clinical signs and CRP levels, although it cannot significantly affect the RT-PCR results or degree of lung involvement. Furthermore, Phyllanthus emblica contains particular bioactive compounds such as chlorogenic acid, quercitrin, myricetin, 7-ketositosterol, quercetin, epigallocatechin, and phyllaemblic, which play an important role in the virus and were most effective in showing the highest binding energy against the protein targets of SARS-CoV-2 and inhibiting the COVID-19 activity by binding to it [40] [41] and [42]. Therefore, the current pharmacoinformatic approach shows a possible role for Phyllanthus emblica in the treatment and management of COVID-19.

Ficus caricais one of several medicinal plants commonly used by folk healers for healing and beneficial treatment, including strengthening people's immunity during the COVID-19 pandemic in Thailand, with survey results showing that the cumulative incidence rate of COVID-19 was low in each area where this herb was used.This is consistent with the findings of Ahmad et al., [25], who discovered that during the COVID-19 pandemic, Ficus carica (tea) was used to treat respiratory disorders alongside antivirals, including anti-allergic drugs [25] and [43]. Terminalia chebulawas one of the most commonly used medicinal plants by folk healers in Thailand during the COVID-19 pandemic, and as evidenced by this survey result, the provinces that used this medicinal plant had a low cumulative COVID-19 incidence. Terminalia chebula waspreviously used in the management of various diseases, and in accordance with the bioactive polysaccharide contained, a study by Nosalova et al. [44] used it as well as an antitussive, and the result showed that cough efforts decreased significantly. Therefore, this medicinal plant is necessary for advancement in development and represents a modern pharmaceutical novelty for COVID-19 treatment. This is consistent with a study by Haque et al., [45] reporting that the medicinal plant Terminalia chebula has established antiviral activity, particularly against viral infections with characteristics similar to those of COVID-19.

Cannabis indica was found to have a significant effect in this study. The area surveyed found the cannabis plant and one of the medicinal herbs used in Thailand. We discovered that during the COVID-19 pandemic, folk healers used this medicinal plant for healing and strengthening immunity in several places in Thailand, and there was a low incidence rate presented in comparison to the cumulative COVID-19 incidence reported in these areas, in accordance with Hussain's et al., [47] study. Assessing the properties of cannabis is significantly more difficult than studying its individual components, and there is still a pressing need for more clinical trials, which would help determine the full potential of this plant both in the case of COVID-19 and many other disorders [46]. Several studies, however, have hypothesized that the cannabis plant contains specific bioactive compounds, such as Phytocannabinoids, that play an important role as well as an anti-inflammatory function in relation to the inflammatory events that occur during severe COVID-19 disease, and that cannabinoids may help to prevent the progression from mild to severe disease [13] [15] [47] and [48]. Furthermore, systemic studies are required to determine the best efficacy and toxic effects, which will be followed by large-scale preclinical trials. Our survey revealed that the proposed plants metabolites can serve as potential anti- SARS-CoV-2 lead molecules for further optimization and drug development processes to combat COVID-19 and future pandemics caused by viruses. This survey will stimulate further analysis by the scientific community and boost antiviral plant-based research followed by novel drug designing.

5. Conclussions

Scientists all around the world are trying to discover the most effective antiviral drug to combat SARS-CoV-2. In this situation, our study emphasized some medicinal plants that folk healers commonly used for healing and that were beneficial for treatment and strengthening the immunity of the people in the area. In the form of a geographical information map, these plants are classified by type of medicinal plant and divided into 11 species, such as Artemisia annua, Harrisonia perforate (Blanco) Merr, Capparis micracantha, Tacca leontopetaloides, Andrographis paniculate, Phyllanthus emblica, Ficus carica, Tiliacora, Terminalia, and Cannabis indica.

Furthermore, a large number of researchers have compiled and created a database of cumulative COVID-19 cases in the country (Thailand); therefore, comparing the cumulative COVID-19 case incidence rate in the scope of the study in 9 provinces, respectively, a significant positive result was found. In addition, this study exercise may lend enough credence to the potential value of Thai medicinal plants (herbs) as possible leads in anti-COVID-19 drug discovery through research and development.

Acknowledgement

The authors would like to thank the grants from office of public health research and innovation administration, Office of Permanent Secretary, Ministry of Public Health, Thailand. Especially Thanks for staff of Provincial Public Health, Health Promotion Hospital. The staff of Subdistrict Health Promotion Hospital for supporting and coordinating to collect the data in the study. We also would like to thank Dr. Peter Scully for GIS map and data development in-part financially supported by the Faculty of Informatics, Mahasarakham University and all who have helped in the research.

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