BIOTROPIA Vol. 30 No. 2, 2023: 183 - 194 DOI: 10.11598/btb.2023.30.2.1784 183 ETHNOBOTANICAL STUDY OF MEDICINAL PLANT USAGE DURING COVID-19 PANDEMIC: A COMMUNITY-BASED SURVEY IN INDONESIA NI MADE DWI MARA WIDYANI NAYAKA1*, PUTU ERA SANDHI KUSUMA YUDA1, DWI ARYMBHI SANJAYA2, DESAK KETUT ERNAWATI3, ERNA CAHYANINGSIH1, NI LUH KADE ARMAN ANITA DEWI1 AND MARIA MALIDA VERNANDES SASADARA1 1Department of Natural Medicine, Faculty of Pharmacy, Universitas Mahasaraswati Denpasar, Denpasar, 80233, Indonesia 2Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Mahasaraswati Denpasar, Denpasar, 80233, Indonesia 3Departement of Pharmacology and Therapy, Faculty of Medicine, Udayana University, Denpasar, 80232, Indonesia Received 21 July 2022 / Revised 1 June 2023 /Accepted 4 June 2023 ABSTRACT Before the availability of a vaccine, Indonesian population relied on traditional medicines to prevent COVID- 19. Any species used by indigenous people could lead to further investigations in modern pharmacology, to preserve ancient knowledge, and to plan for plants’ conservation. The study aimed to discover and record species, methods of preparation, route of administration, and motivation in using medicinal plants by the Indonesian population during the COVID-19 pandemic. Participants of survey were selected from the people who live in Java and Bali for responding to an online structured questionnaire. Relative Frequency of Citation (RFC) was employed in the quantitative analysis of the collected data. The pharmacological relevance of the five plants with the highest RFC was further reviewed. The results showed that respondents used 59 plants from 28 families. Five species with the highest RFC were Curcuma longa (0.707), Zingiber officinale (0.674), Cymbopogon citratus (0.269), Kaempferia galanga (0.174), and Curcuma zanthorrhiza (0.165). Most plants were prepared by boiling (77.97%) and administered orally as a single ingredient or mixed with other herbals. Respondents believed that the plants were beneficial as immune-booster (71.26%), maintain good health (24.85%) and stamina (12.28%), and prevent viral infection, including COVID-19 (5.39%). The most commonly used plants might be scientifically based to boost immunity. However, their usage against COVID-19 and the medicinal value of herbal mixtures should be further investigated. Keywords: COVID-19, Ethnobotany, Indonesia, Medicinal plants INTRODUCTION Corona Virus Disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). It was found in China in December 2019 and spread to other countries, including Indonesia. The first two confirmed COVID-19 cases in Indonesia were reported on March 2, 2020, and the numbers keep rising since then (Djalante et al. 2020). Based on history, previous SARS-CoV coronavirus also caused an outbreak in China in 2003. The genetic sequence analysis showed that SARS-CoV-2 was similar around 79% to SARS- CoV. Thus, most of the studies on its prevention and medication were adopted from the previous outbreak (Ghaffari et al. 2020). The Indonesian Ministry of Health released health protocols to prevent and control COVID-19 (HK.01.07/MENKES/382/2020), which included the suggestion to wear masks, washing hands frequently, social distancing, and immunity enhancement through clean and healthy living behavior. During the SARS outbreak, natural medicine showed beneficial effects in preventing and treating patients, particularly in high-risk subjects (Boozari & *Corresponding author, email: nimade.nayaka@unmas.ac.id; nimade.nayaka@gmail.com BIOTROPIA Vol. 30 No. 2, 2023 184 Hosseinzadeh 2020; Y. Li et al. 2020). The usage of medicinal plants as a prophylaxis measure against COVID-19 was also recommended by Ayurveda and Traditional Chinese Medicine (Boozari & Hosseinzadeh 2020; Khanal et al. 2020; Vellingiri et al. 2020). Further, many studies have proven the antiviral, anti- inflammatory, and immunomodulatory properties of medicinal plants that are potentially helpful to combat viral diseases (Lin et al. 2014; Khanna et al. 2020). Indonesia has abundant natural resources in plant species and the local people have used them as herbal remedies. Some of the ethnobotanical studies recorded the importance of Indonesian biodiversity as traditional medicines in different health conditions (Nahdi & Kurniawan 2019; Taek et al. 2019; Jadid et al. 2020). Those studies are significantly important to converse precious indigenous knowledge and publish them as academic literature. In the present study, we conducted an online survey to identify the use of medicinal plants by the Indonesian population during the COVID-19 pandemic. The comprehensive data from respondents on the species of medicinal plants, method of preparation and administration, as well as motivation to use, were documented. While antivirus and vaccines are vital, the research on natural medicine regarding COVID-19 may be used as a reference to develop new drug candidates and as home- based remedies in the future that are inexpensive, commonly, and easily implemented in society. The study aimed to discover and to record species, methods of preparation, route of administration, and motivation in using medicinal plants by the Indonesian population during the COVID-19 pandemic. MATERIALS AND METHODS Study Area A survey was conducted in Java and Bali Island (Figure 1), which consist of 7 provinces, namely Special Capital Region of Jakarta (6°12′S, 106°49′E), Banten (6°30′S 106°15′E), West Java (6°45′S 107°30′E), Central Java (7°30′S 110°00′E), Special Region of Yogyakarta (7°47′S 110°22′E), East Java (7°16′S 112°45′E), and Bali (8°20′06″S 115°05′17″E). All the regions have diverse ethnicities such as Bantenese in Banten, Balinese in Bali, and Javanese in other regions. Respected to the ethnicity, each of the regions has its traditional language. However, natives speak Indonesian in their daily lives. Figure 1 Study area of the ethnobotanical survey in 7 provinces in Indonesia Medicinal Plants Usage During COVID-19 in Indonesia – Nayaka et al. 185 Data Collection A cross-sectional study was undertaken using a self-administered and structured questionnaire. The questionnaire consisted of three parts that aimed to collect the respondents demographic characteristics, medicinal plants data, and respondents’ motivation using the plants during the pandemic. The data collection was carried out by online survey from June to August 2020. The questionnaire was in Indonesian and examined by two experts in pharmacy and Bahasa Indonesia fields then piloted among 30 participants to ensure its validity before being used to collect data. A guide to estimate the minimum sample size of respondents required for this study based on the formula (Pourhoseingholi et al. 2013). n = z2 p(1 – p) d2 Where: Z = The statistic corresponding to level of …….confidence. P = Expected prevalence of COVID-19. d = Precision. In this study, the respondents included indigenous people living in Java and Bali islands and consuming medicinal plants during the COVID-19 pandemic in Indonesia. The respondents’ motivation to use the plants was also recorded. Any dubious data that could not be confirmed was excluded. The questionnaire and methodology for this study were approved by the Faculty of Medicine, Udayana University (Ethics approval number: 1195/UN14.2.2.VII.14/LT/2020). Plant Identification The scientific names of medicinal plants reported by respondents were determined using cross-references between their local names and database in Indonesian Herbal Pharmacopeia, Indonesian Herbal Formulary (PERMENKES NO.6/2016), and Indonesian Traditional Medicine Formulary (HK.01.07/MENKES/ 187/2017). Herbal specimens could not be collected due to the strict travel restrictions regulated by the Indonesian government during the COVID-19 pandemic in the study area. The scientific names of the reported plants were checked with The Plant List website (accessed on January 8, 2021, http://www.theplantlist.org). Data Analysis The collected data were evaluated by using Microsoft Office Excel (2016) spreadsheets. Further, quantitative data analysis to show the local importance of each plant species was demonstrated by using the relative frequency of citation (RFC) (Aziz et al. 2017). with the formula below: RFC = FC/N (0 < RFC < 1) Where: FC = Number of informants mentioning a ………particular species. N = Total number of respondents RESULTS AND DISCUSSION Indonesia is an inhabitant of about 80% of the world’s medicinal plants which local people use to prevent and cure many ailments (Elfahmi et al. 2014). In the current study, an online survey was conducted to collect data regarding medicinal plant usage by Indonesian during the COVID-19 pandemic. The respondents were limited to those who were native and living in 8 provinces in the two most densely populated islands in Indonesia (Java and Bali islands) (Table 1). Moreover, based on the Indonesian government’s official website (www.covid19.go.id), most of the confirmed COVID-19 cases were located in both islands and the prevalence reached 82.2%. Based on the prevalence of COVID-19 and the statistic corresponding to the level of confidence is 1,96 with a precision of 5%, the minimum number of respondents for this study was 224 respondents. However, in this study, 344 respondents participated and this number exceeded the minimum sample. As shown in Table 1, 82.04% (274) of respondents were female. This result is in line with several studies (Villena-Tejada et al. 2021; Brahmi et al. 2022; Odebunmi et al. 2022). Which indicated the domination of females in using medicinal plants. This predominance is probably related to several factors such as women being more familiar with medicinal plants because they BIOTROPIA Vol. 30 No. 2, 2023 186 are also being used as cooking ingredients. Correspondingly, in most populations, women are believed to bear the responsibility for the family health needs causing them to be more informed about using medicinal plants than their male counterparts (Torres-Avilez et al. 2016). In the current study, most of the respondents came from the Province of Bali. A Hindu-most populated area in Indonesia (Statistics Indonesia 2010). The Balinese are well known for their local wisdom called Usada, a traditional medicine inspired by the Hindu holy book Ayurveda (Muderawan et al. 2020). Age is another sociodemographic factor contributing to the use of medicinal plants. Several studies found that older age was the main user of traditional medicine (Rahayu et al. 2020). On the contrary, 67.37% (225) of respondents in this study were 20 to 40 years old. Indicating the younger age group was also interested in using medicinal plants during the pandemic of COVID-19. Similar survey studies conducted in Algeria and Morocco during the pandemic also showed similiar results (Belmouhoub et al. 2021; Brahmi et al. 2022; Chebaibi et al. 2022). Table 1 Demographic characteristics of respondents Characteristic Number of Respondents (n = 334) Percentage (%) Gender Male 60 17.96 Female 274 82.04 Province of Origin Special Capital Region of Jakarta 13 3.89 Banten 2 0.60 West Java 35 10.48 Central Java 8 2.40 East Java 24 7.19 Special Region of Yogyakarta 6 1.80 Bali 246 73.65 Age (years) < 20 35 10.48 20 – 40 225 67.37 > 40 74 22.16 Religion Islam 66 19.76 Hindu 247 73.95 Protestant 12 3.59 Catholic 8 2.40 Buddha 1 0.30 Table 2 Medicinal plants used by respondents during the COVID-19 pandemic in Indonesia Family Scientific Names Local Names (Indonesia) Common Names (English) Part used Method of Preparationa RFCb Motivation of usec Reported fromd Acanthaceae Andrographis paniculata (Burm.f.) Nees Sambiloto Green chiretta Leaves Boil 0.030 A, B, D, E 1, 5, 7 Amaryllidaceae Allium cepa L. Bawang merah Shallot Bulb Boil, burning, eaten directly 0.006 B 6,7 Allium sativum L. Bawang putih Garlic Bulb Eaten directly 0.063 A-E 3-7 Anacardiaceae Spondias pinnata (L.f) Kurz. Cemcem Common hog-plum Leaves Cold infusion 0.006 B 7 Annonaceae Annona muricata L. Sirsak Soursop Leaves Boil 0.015 A-D 3,7 Apiaceae Apium graveolens L. Seledri Celery Leaves Boil 0.003 B 3 Centella asiatica (L.) Urb. Pegagan Asiatic pennywort Leaves Boil, eaten directly 0.021 A,B,D,E 7 Coriandrum sativum L. Ketumbar Coriander Fruit Boil 0.012 A,B,D,E 3, 5, 7 Foeniculum vulgare Adas Fennel Fruit Boil 0.003 B 4 Medicinal Plants Usage During COVID-19 in Indonesia – Nayaka et al. 187 Family Scientific Names Local Names (Indonesia) Common Names (English) Part used Method of Preparationa RFCb Motivation of usec Reported fromd Mill. Arecaceae Cocos nucifera L. Kelapa Coconut Fruit (water & oil) Eaten directly 0.009 B 7 Asteraceae Blumea balsamifera (L.) DC. Sembung Buffalo-ear Leaves Boil 0.006 B,D 7 Gynura procumbens (Lour.) Merr. Sambung nyawa Longevity spinach Leaves Boil 0.003 B 6 Pluchea indica (L.) Less. Beluntas Indian camphorweed Leaves Boil 0.009 B 7 Sonchus arvensis L. Tempuyung Perennial Sow-thistle Leaves Boil 0.003 B 7 Basellaceae Anredera cordifolia (Ten.) Steenis Binahong Gulf madeiravine Leaves Boil 0.003 B 1 Caricaceae Carica papaya L. Pepaya Papaya Leaves Boil 0.003 E 3 Fabaceae Caesalpinia sappan L. Secang Brazilwood Wood Boil 0.027 A-E 3-7 Clitoria ternatea L. Bunga telang Asian pigeonwings Flower Boil 0.009 A,D 5, 7 Erythrina variegata L. Dadap Tiger’s claw Leaves Boil 0.003 A,D 7 Tamarindus indica L. Asam jawa Tamarind Fruit Boil 0.060 A-E 1, 3-7 Lamiaceae Mentha piperita L. Pipermin Peppermint Leaves Hot infusion 0.009 A,B,D,E 2, 3, 7 Peronema canescens Jack Sungkai False elder Leaves Boil 0.003 B 3 Lauraceae Cinnamomum burmanni (Nees & T.Nees) Blume Kayu manis Batavia cinnamon Bark, Leaves Boil, burning, cold and hot infusion 0.114 A-E 1-7 Malvaceae Hibiscus sabdariffa L. Rosela Roselle Flower Boil 0.003 B 7 Meliaceae Azadirachta indica A.Juss Mimba Neem Leaves Eaten directly 0.003 B 7 Moraceae Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg Sukun Breadfruit Leaves Boil 0.003 B 7 Moringaceae Moringa oleifera Lam. Kelor Drumstick tree Leaves Boil, hot infusion 0.045 A-E 3-7 Myrtaceae Melaleuca cajuputi Powell Kayu putih Cajuput Oil N/A 0.003 C 1,7 Syzygium aromaticum (L.) Merr. & L.M.Perry Cengkeh Clove Flower Boil, hot infusion 0.048 A-E 2-7 Syzygium polyanthum (Wight) Walp. Salam Indonesian bay leaf Leaves Boil 0.021 A-E 3, 5-7 Oleaceae Olea europaea L. Zaitun Olive Fruit (Oil) Eaten directly 0.003 B 3 Pandanaceae Pandanus amaryllifolius Roxb. Pandan Pandan Leaves Boil 0.003 A,D 2 Phyllanthaceae Sauropus androgynous (L.) Merr. Katuk Sweet leaf Leaves Cold and hot infusion 0.021 A,B,D,E 7 Phyllantus niruri L. Meniran Gale of the wind Leaves Boil, hot infusion 0.009 A,B 5, 7 Piperaceae Piper betle L. Sirih Betel Leaves Boil, eaten directly 0.072 A-E 1, 3 Piper crocatum Ruiz & Pav. Sirih merah Celebes pepper Leaves Boil 0.072 B 7 Piper nigrum L. Lada Black pepper Seed Boil 0.003 B 3 Piper retrofractum Vahl Cabai jawa Javanese long pepper Fruit Boil 0.003 E 7 Poaceae Cymbopogon citratus (DC.) Stapf. Serai dapur Lemongrass Stem, Leaves Boil, hot infusion 0.269 A-E 1-7 Oryza sativa L. Beras Rice Starch Cold infusion 0.024 A,B,D,E 3-7 Ranunculaceae Nigella sativa L. Jintan hitam Black seed Seed Boil 0.012 A,B,E 3, 5, 7 Rutaceae Citrus aurantiifolia (Christm.) Swingle Jeruk nipis Egyptian lime Fruit Juiced, boil, hot and cold infusion 0.177 A-E 1-7 Citrus hystrix DC. Jeruk purut Kaffir lime Leaves, Fruit Boil 0.006 B,E 6 Citrus limon (L.) Osbeck Lemon Lemon Fruit Cold and hot infusion 0.108 A-E 1, 3-5, 7 Citrus reticulata Jeruk Mandarin Fruit Eaten directly 0.021 A,B,E 4, 7 BIOTROPIA Vol. 30 No. 2, 2023 188 Family Scientific Names Local Names (Indonesia) Common Names (English) Part used Method of Preparationa RFCb Motivation of usec Reported fromd Blanco Rubiaceae Morinda citrifolia L. Mengkudu Noni Fruit Juiced 0.015 B-D 7 Schisandraceae Illicium verum Hook.f. Bunga lawang Star anise Flower Boil 0.009 A,B,E 4, 5, 7 Theaceae Camellia sinensis (L) Kuntze Teh Tea plant Leaves Boil, hot infusion 0.012 B-D 1, 3, 7 Zingiberaceae Alpinia galanga (L) Willd. Lengkuas Greater galangal Rhizome Boil, hot infusion 0.054 A-E 1, 4, 5, 7 Boesenbergia pandurata (Roxb.) Schltr. Temu kunci Chinese keys Rhizome Boil 0.006 B,E 7 Curcuma longa L. Kunyit Turmeric Rhizome Boil, burning, hot infusion 0.707 A-E 1-7 Curcuma zanthorrhiza Roxb. Temulawak Javanese turmeric Rhizome Boil, hot infusion 0.165 A-E 1-7 Curcuma zedoaria (Christm.) Roscoe Temu putih Zedoary Rhizome Boil 0.006 A,D,E 5, 7 Amomum compactum Sol. ex Maton Kapulaga Javanese cardamom Seed, flower Boil, hot infusion 0.018 B,D,E 3, 5, 7 Kaempferia galanga L. Kencur Cutcherry Rhizome Boil, burning, hot infusion 0.174 A-E 1-7 Kaempferia rotunda L. Kunyit putih Peacock ginger Rhizome Juice, hot infusion 0.021 A,B,D,E 5, 7 Zingiber officinale Roscoe Jahe Ginger Rhizome Boil, burning, hot infusion 0.674 A-E 1-7 Zingiber officinale var.rubrum Theilade Jahe merah Red ginger Rhizome Boil, hot infusion 0.039 A,B,D,E 3, 5-7 Zingiber zerumbet (L.) Roscoe ex Sm. Gamongan /lempuyang gajah Bitter ginger Rhizome Boil 0.003 E 7 Notes: aAll plants were prepared with water and administered orally, except cajuput by inhalation. bRFC = Relative Frequency of Citation, cA = to keep healthy, B = to boost the immune system, C = to avoid virus infection, including COVID-19, D = to build stamina, E = other, d1 = Special Capital Region of Jakarta, 2 = Banten, 3 = West Java, 4 = Central Java, 5 = East Java, 6 = Special Region of Yogyakarta, 7 = Bali, N/A = not available, Table 3 Plants mixtures used by respondents during the COVID-19 pandemic in Indonesia Plants Mixture No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 A. sativum - - - - - - - - - - - + - - - - - - - - - - - - - - - - - - - - - C. asiatica - - - - - - - - - - - - - - + - - - - - - - - - - - - - - - - - - C. nucifera - - + - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - P. indica - - - + - - - - - - - - - - - - - - - - - - - - - - - - - - - - - T. indica - - - - + - - - - - - - - - + - - - - + - - - - - - - - + - - - - C. burmanni - - - - - - - - - - - - - - - - + - - - - - - - - - - - - + - - - S. aromaticum - - - - - - - - - - - - - - - - - - - - - - - - - - - + - - - - - P. amaryllifolius - - - - - - - - - - - - - + - + - - - - - - - - - - - - - - - - - P. betle - - - - - - - - - - - - - - - - - - - + - - - - - - - - - - - - - C. citratus - - - - - - - - - + - - - - - - - - - - - - - - + + + + + - + + - O. sativa - - - - - - - - + - - - - - - - - - - - - - - - - - - - - - C. aurantiifolia - - - - - + - - - - - + + - - - - - + - + - + - - + - - - - - + - C. lemon + - - - - - + - - - + - - - - - - - - - - - - + - - + - - - - - - C. sinensis + + - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - A. galangal - - - - - - - - - - - - - - - - - - - - + - - - - - - - - - - - - C. longa - - + + + + + + - - - - - - - - + + + + + + + + + - - - + + + + + C. zanthorrhiza - - - - - - - - - - - - + + - - - - - - + + - - - - - - + + - + K. galangal - - - - - - - - + - - - - - - + - + - - - - - - - - - - - - - - + K. rotunda - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Z. officinale - + - - - - - + - + + - - - - - + + + - - + - + + + + + + + + + + Total plants mixed 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 Notes: + = plants available in mixtures. * All mixtures were prepared by boiling and administered orally Medicinal Plants Usage During COVID-19 in Indonesia – Nayaka et al. 189 Table 3 Plants mixture used by respondents during the COVID-19 pandemic in Indonesia (continued) Plants Mixture No.* 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 C. asiatica - - - - - - - - - - - - - - - + + - - - - - - - - - - - - - C. sativum - - - - - - - - - - - - - - - - - - - - - - - - - - + - - - F. vulgare - - - - - - - - - - - - - - - - - - - - - - - - - - - - + - C. sappan - - - - - - - - - - - - - + - - - - - - + - - - + - - + + - C. ternatea - - - - - - - - - - - - - - - - + - - - - - - - - - - - - - T. indica - - - - - - - - - - - + - - - - - - + - - - - - - + - - - - M. Piperita - - - - - - - - - - - - - - - - - - - - - - - + - - - - - - P. canescens - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - C. burmanni - - - - - - + - + + - - - + - - - - - + - - + + - + + - + - A. altilis - - - - - - - - - - + - - - - - - - - - - - - - - - - - - - S. aromaticum - - - - - - - - - + - - + - - - - - - + - + - - - + + - + - S. polyanthum - - - - - - - - - - - - - - - - - + - - - - - - - - - - - - O. europea - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - P. amaryllifolius - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - S. androgynous - - - - - - - - + - - - - - - - - - - - - - - - - - - - - - P. niruri - - - - - - + - - - - - - - - - - - - - - - - - - - - - - - P. betle - - - - - - - - - - - + - - - - - - + - - - - - - - - - - + P. crocatum - - - - - - - - - - - - + - - - - - - - - - - - - - - - - P. retrofractum - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + C. citratus - - - - + + - - - + - + - + + + + + + + + + + + + + + + - + C. aurantiifolia - + + - + - - - - - - - - - + - - - - - - - + + - - - + - C. lemon - - - - - - - - - - - - - - - - + - - - - - - - + - - - - - I. verum - - - - - - - - - - - - - - - - - - - - - - - - - - - + - A. Galanga + - - + - - - - - - - - - - + - - - - - - - - - + - - - - - B. pandurate - - - - - - - - - - - - - - - - - - - - - - - - - - - - + C. longa + + + + + + + + + - - + + + + + - - + + + + + + + + + + + + C. zanthorrhiza - - - - - - - + - - + - + - - + - + - - + + + - - + - + - + C. zedoaria - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - A. compactum - - - - - - - - - - - - + - - - - - - - - - + - - - - + - - K. galangal + + + + - + - + + - - - - - - - - - + + + + - - - - + + + + K. rotunda - - - - - - - - - + - - - - - - + - - - - - - - - - + - + Z. officinale + + + + + + + + - + - + - + + + + + + + + + + + + + + + + + Z. officinal var. rubrum - - - - - - - - - - + - - - - - - - - - - - - - - - - - - - Z. zerumbet - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + Total plants mixed 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 6 6 6 6 6 6 7 7 7 8 9 10 Notes: + = plants available in mixtures. * All mixtures were prepared by boiling and administered orally Table 4 Method of preparation for medicinal plants used during the COVID-19 pandemic in Indonesia Category Frequency %* Boil 46 77.97 Eaten directly 6 10.17 Cold Infusion 18 30.51 Hot Infusion 8 13.56 Burning 5 6.78 Notes: *some of the plants were prepared by more than one method. Thus, the total percentage may not add up to 100%. Table 5 The motivation for medicinal plants used by respondents during the COVID-19 pandemic in Indonesia Category Frequency %* to boost the immune system 238 71.26 to keep healthy 83 24.85 to build stamina 41 12.28 other motives 41 12.28 to prevent virus infection, including COVID-19 18 5.39 Notes: *some respondents reported more than one reason for herbal use. Thus, the total percentage may not add up to 100%. BIOTROPIA Vol. 30 No. 2, 2023 190 The present study revealed that respondents used 59 species of medicinal plants from 28 families (Table 2) both singly or in herbal mixtures (Table 3). Additionally, most of the plants were prepared by boiling and then consumed orally (Table 4). Indonesian traditional medicine in the form of polyherbal drinks has existed for generations so called loloh (in Bali) and jamu (in Java). Some of the reported plants in the present study that are also used in loloh formulation namely S. pinnata, B. balsamifera, E. variegata., C. burmanni, C. asiatica, A. indica, P. amaryllifolius, P. niruri, S. androgynous, P. betle, C. aurantiifolia, C. zanthorrhiza, K. rotunda, Z. officinale, and Z. zerumbet (Sujarwo et al. 2015). Similarly, other reported plants were commonly available in jamu formula such as C. verum, C. aurantifolia, Z. officinale var. Rubrum, T. indica, A. galanga, C. longa, C. zanthorrhiza, P. niruri. K. galanga, O. sativa, and P. amaryllifolius (Elfahmi et al. 2014; Hartanti et al. 2020). These plants were empirically used for various medicinal purposes (Elfahmi et al. 2014; Sujarwo et al. 2015). Further, the current study revealed that respondents consumed Jamu Kunyit Asam and Jamu Beras Kencur during the pandemic (Table 3, Mixture No. 5 and No. 9, respectively). The composition of herbal mixtures could be varied according to individual preferences and local recipes. For example, Mixture No.20, 29, 45, 52, and 59 in Table 3 showed the variation of Jamu Kunyit Asam. However, there was limited data related to the efficacy of the modified version of jamu formula. Further research should be conducted to support the use of those herbal mixtures in term of efficacy test. Most respondents believed that the plants’ consumption was beneficial during the pandemic because they could enhance immunity, maintain health and stamina, and prevent viral infection (Table 5). A study showed that the interest in and use of immune- related herbals worldwide increased during the COVID-19 pandemic (Hamulka et al. 2020). Other ethnopharmacological studies confirmed the usage of medicinal plants such as A. cepa, A. sativum, C. asiatica, C. papaya, T. indica, C. burmanni, and C. longa to boost immunity by traditional healers and society in various health conditions (Siew et al. 2014; Anywar et al. 2020; Oladele et al. 2020; Lin et al. 2021). Meanwhile, review studies confirmed the benefit of natural immune enhancer intakes such as A. panniculata, A. sativum, M. piperita, M. cajuputi essential oil, C. sinensis, N. sativa, and Z. officinale to prevent COVID-19 and improve overall patient health (Boozari & Hosseinzadeh 2020; Sen et al. 2020; Silveira et al. 2020). Some of the medicinal plants reported in the current study have been also recommended by the Indonesian Ministry of Health (HK.02.02/IV.2243/2020) to maintain well- being and prevent illness during the pandemic. In the official announcement, six herbal mixtures consisting of Z. officinale var. rubrum, C. aurantiifolia, C. verum, C. longa, A. galanga, C. asiatica, C. zanthorrhiza, K. galanga, P. amaryllifolius, M. oleifera, and A. sativum. The mixtures were recommended to boost the immune response and also have similar preparation and administration methods as reported in this study. Likewise, C. longa, Z. officinalle, C. verum, and P. nigrum also have been recommended by the Indian Ministry of AYUSH (Ayurveda, Yoga, and Naturopathy, Unani, Siddha, and Homeopathy) to boost immunity as a prophylaxis measure against COVID-19 (Khanal et al. 2020). The beneficial effect of medicinal plants as immune-enhancer against COVID-19 should be confirmed scientifically. In viral diseases, the infection could be fought by the host's immune response. When viruses infect the host cells, innate immunity blocks virus replication, promotes virus clearance, stimulates tissue repair, and activates a prolonged adaptive immunity (G. Li et al. 2020). Moreover, viral infection and inflammation of lung tissues are observed in COVID-19. Thus, the antiviral and inflammatory activities of medicinal plants are essential properties to combat COVID-19 (Khanal et al. 2020). On the other hand, it should be noticed that the immune system is complicated and highly regulated by numerous molecular and cellular events. Therefore, immunity enhancement may be either valuable or destructive to the organism, depending on the overall degree of modulation and the pathophysiological condition (Gertsch et al. 2011). Based on the calculation of RFC, five plants had the highest scores: C. longa, Z. officinale, C. Medicinal Plants Usage During COVID-19 in Indonesia – Nayaka et al. 191 citratus, K. galanga, and C. zanthorrhiza. Therefore, further literature review in the current study was highlighted for those plants. Turmeric (C. longa) contains curcumin, a polyphenol with various pharmacological actions. The compound showed immunomodulation activity through several mechanisms, especially by regulating inflammatory factors (Tasneem et al. 2019; Behl et al. 2021). Likewise, the polysaccharide extract from turmeric could enhance the immune system (Yue et al. 2010). A computational study regarding anti-SARS-CoV-2 showed that curcumin exhibited a high potency to block the virus's main protease (C19Mpro), which plays an important role in the viral replication process. Curcumin had lower binding energy to C19Mpro than other compounds from P. nigrum, Z. officinale, N. sativa, S. aromaticum, A. sativum and A. cepa (Ibrahim et al. 2020). Ginger (Z. officinale) contains some compounds with anti-inflammatory and immunomodulatory activities such as 6-gingerol, 6-shogaol, zingerone, and 6-paradol (Choi et al. 2018). An alcohol extract was reported to induce phagocytosis by macrophages in mice while crude extract increased humoral and cell- mediated immune responses (Gautam et al. 2020). Meanwhile, another molecular docking evaluation showed the ability of zingiberene, 6- gingerol, zingerone, gingerenone-A, 6-shogaol, and 6-dehydrogingerdione to block C19Mpro. But their potencies were considerably low due to higher binding energies than N3 inhibitor as control (Garg et al. 2020). An in vivo and in vitro study revealed the immunomodulatory effect of water extract and essential oil from lemongrass (C. citratus). The water extract with linalool oxide and epoxy- linalool as major compounds could prevent the production of IL-1β but induce IL-6 production by macrophages. Meanwhile, its essential oils which contained neral and geranial could inhibit cytokine production in vitro (Sforcin et al. 2009). Moreover, geraniol, another compound in its essential oil, inhibited the S1 subunit in spike proteins of SARS-CoV-2 through a docking simulation (Wani et al. 2020). The rhizome part of cutcherry (K. galanga) is rich in bioactive compounds such as ethyl-p- methoxycinnamate and diarylheptanoids with anti-inflammatory and immunomodulation activity (Jagadish et al. 2016; Yao et al. 2018). Its polysaccharides isolate enhanced the immunoregulation capability of CD4+ T cells (Yang et al. 2018). Furthermore, a computational study exhibited the activity of its bioactive compounds (kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives) to block the 3a channel protein of SARS-CoV. Inhibition of this channel would inactivate virus production and allow the host to build up its immunity system (Schwarz et al. 2014). Another docking investigation indicated that kaempferol, due to its hydroxyl, ketone, and ether groups, was a stronger C19Mpro inhibitor than other tested natural compounds (Khaerunnisa et al. 2020). The crude polysaccharide extract of Javanese turmeric (C. zanthorrhiza) could enhance the immune system by activating of NF-kappaB (Kim et al. 2007). Xanthorrhizol and C. xanthorrhiza extract significantly inhibited the production of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6 and - 1𝛽, and C-reactive protein (Kim et al. 2014). Moreover, curcumin, demethoxycurcumin, and bisdemethoxycurcumin in C. xanthorrhiza (similar compounds also contained in C. longa) showed their potential as C19Mpro inhibitors (Khaerunnisa et al. 2020; Sumaryada & Pramudita 2020). However, another study revealed that their inhibition actions were lower than nelfinavir, a protease inhibitor used as a drug standard (Khaerunnisa et al. 2020). Meanwhile, another docking investigation on the similarity of active sites exposed that bisdemethoxycurcumin had a greater ability to inhibit the binding pocket of C19Mpro than N3 inhibitor, as the control ligand (Sumaryada & Pramudita 2020). Other plants with lower RFC values (Table 2) such as A. galanga and A. paniculata, Citrus sp., C. sinensis, S. androgynous, F. vulgare, O. europea, and A. graveolens also confirmed to have immunomodulatory properties and potential against COVID-19 (Elfahmi et al. 2014; Khaerunnisa et al. 2020; Utomo et al. 2020). Regarding COVID-19, most of the antiviral studies of medicinal plants and their compounds were based on computational methods and resulted in a preview of their potential against COVID-19. Though some of the reported medicinal plants showed low molecular potency in blocking target sites, it is necessary to BIOTROPIA Vol. 30 No. 2, 2023 192 highlight that the immunomodulatory actions support their beneficial role during the COVID- 19 pandemic. Further pre-clinical and clinical investigations are needed to warrant their efficacy as health-promoting agents against COVID-19. These ethnobotany research results may be necessary to anticipate another trans- boundary animal or plant diseases pandemic by studying their bioactive compound for pharmacopeia studies in more detail. CONCLUSION During the COVID-19 pandemic, there were 59 medicinal plants belonging to 28 families used by Indonesian. The plants were prepared mainly by boiling and administered orally. Based on the RFC value, the most important plants were C. longa, Z. officinale, C. citratus, K. galanga, and C. zanthorrhiza. Also, respondents believed that those plants could boost immunity, maintain health and stamina, and prevent COVID-19. In general, the medicinal plants reported in the current studies were confirmed by scientific literature to be beneficial as immune-booster during the COVID-19 pandemic. Meanwhile, their ability to block SARS-CoV-2 infection was mainly studied only through molecular docking evaluations. More research should be conducted to ensure their potency against SARS-CoV-2 and their efficacy when used as a single ingredient or in mixtures with other herbs. Also, actions should be taken to preserve the community’s traditional knowledge of using medicinal plants. 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