biomolecules Review Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities Ari Satia Nugraha 1,* , Bawon Triatmoko 1 , Phurpa Wangchuk 2 and Paul A. Keller 3,* 1 Drug Utilisation and Discovery Research Group, Faculty of Pharmacy, University of Jember, Jember, Jawa Timur 68121, Indonesia; [email protected] 2 Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia; [email protected] 3 School of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, and Illawarra Health & Medical Research Institute, Wollongong, NSW 2522 Australia * Correspondence: [email protected] (A.S.N.); [email protected] (P.A.K.); Tel.: +62-3-3132-4736 (A.S.N.); +61-2-4221-4692 (P.A.K.) Received: 17 December 2019; Accepted: 21 January 2020; Published: 24 January 2020 Abstract: This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations. Keywords: epiphytes; medicinal plants; phytochemistry; pharmacology; drug leads 1. Introduction Epiphytes are plants that grow on other plants and are often known as air plants. They are mostly found in moist tropical areas on canopy tree-tops, where they exploit the nutrients available from leaf and other organic debris. These plants exist within the plantae and fungi kingdom. The term epiphyte itself was first introduced in 1815 by Charles-François Brisseau de Mirbel in “Eléments de physiologie végétale et de botanique” [1]. Epiphytes can be categorized into vascular and non-vascular epiphytic plants; the latter includes the marchantiophyta (liverworts), anthocerotophyta (hornworts), and bryophyta (mosses). The common epiphytes are mosses, ferns, liverworts, lichens, and the orchids. Epiphytes fall under two major categories: As holo- and hemi-epiphytes. While orchids are a good example of holo-epiphytes, the strangler fig is a hemi-epiphyte. Although geological studies have proposed the existence of epiphytes since the pleistone epoch, an epiphyte was first depicted in “the Badianus Manuscript” by Martinus de la Cruz in 1552, which showed the Vanilla fragrans, a hemi-epiphytic orchid, being used by the tribal communities in latin America for fragrance and aroma, usually hung around their neck [1]. Biomolecules 2020, 10, 181; doi:10.3390/biom10020181 www.mdpi.com/journal/biomolecules Biomolecules 2020, 10, 181 2 of 66 Biomolecules 2020, 10, x 2 of 57 Epiphytes have been a source of of food food and and medicine medicine for for thousands thousands of of years. years. Since Since they they grow grow in in a aunique unique ecological ecological environment, environment, they they produce produce in interestingteresting secondary secondary metabolites metabolites that that often show exciting biologicalbiological activities.activities. There There are are notable notable reviews on non-vascular epiphytes, bryophyta, regardingregarding theirtheir phytochemicalphytochemical andand pharmacologicalpharmacological activitiesactivities [[2–5].2–5]. There are also extensive reviews on epiphyticepiphytic lichenslichens coveringcovering secondarysecondary metabolitesmetabolites andand theirtheir pharmacologicalpharmacological activitiesactivities [[6–9].6–9]. The only availableavailable reviewreview on on vascular vascular epiphytes epiphytes related related to medicinalto medicinal uses uses was was focused focused on Orchidaceae on Orchidaceae [10]. Therefore,[10]. Therefore, to the to best the of best our knowledge,of our knowledge, there is nothere extensive is no extensiv databasee database of vascular of epiphytesvascular epiphytes regarding theirregarding medicinal their contribution.medicinal contribution. There areare 27,614 27,614 recorded recorded species species of of vascular vascular epiphytes epiphytes belonging belonging to73 to families73 families and and 913 genera913 genera [11]. Vascular[11]. Vascular epiphyte epiphyte species arespecies commonly are commonl found iny pteridophyta,found in pteridophyta, gymnosperms, gymnosperms, and angiosperms and plantangiosperms groups, plant which groups, are mostly which found are mostly in the found moist tropicalin the moist areas tropical on canopy areas tree on canopy tops, where tree tops, they exploitswhere they the exploits nutrients the available nutrients from available leaf and from other leaf organic and other debris organic [12,13 debris]. In this [12,13]. study, In information this study, oninformation vascular epiphyticon vascular medicinal epiphytic plant medicinal species plan wast species collected was using collected search using engines search (Web engines of Science, (Web Scifinderof Science, Scholar, Scifinder prosea, Scholar, prota, prosea, Google prota, scholar), Google medicinal scholar), plant medicinal books (Plant plant Resourcesbooks (Plant of South-EastResources Asia:of South-East Medicinal Asia: and PoisonousMedicinal Plantsand Poisonous [14–16], Plant Plants Resources [14–16], of Plant South-East Resources Asia: of Cryptogams: South-East FernsAsia: andCryptogams: Fern Allies Ferns [17], and Mangrove Fern Allies Guide [17], for South-EastMangrove AsiaGuide [18 for], MedicinalSouth-East Plants Asia of[18], the Medicinal Asia-Pacific Plants [19], Medicinalof the Asia-Pacific Plants of the[19], Guiana Medicinal [20], IndianPlants Medicinal of the Guiana Plants [[20],21,22 ],Indian Medicinal Medicinal Plants ofPlants Bhutan [21,22], [23], Medicinal Plants and aromatic of Bhutan plants [23], Medicinal of Indian and Ocean aromatic islands: plants Madagascar, of Indian Ocean Comoros, islands: Seychelles Madagascar, and MascarenesComoros, Seychelles [24]), and theand Indonesian Mascarenes Medicinal [24]), and Plants the Database Indonesian [25 ].Medicinal Scientific namesPlants ofDatabase the epiphytic [25]. medicinalScientific names plant species of the wereepiphytic compared medicinal against plant the Plantlistspecies databasewere compared for accepted against names the toPlantlist avoid redundancydatabase for [26accepted]. The time-frame names to avoid threshold redundancy for data coverage[26]. The wastime-frame from the threshold earliest available for data datacoverage until earlywas from 2020. the Nevertheless, earliest available empirical data knowledgeuntil early 2020. regarding Nevertheless, traditional empirical medicinal knowledge plants was regarding passed throughtraditional generations medicinal plants using was verbal passed or written through communication, generations using with verbal verbal or written communication communication, highly practicedwith verbal by remotecommunication tribes [27 ,highly28]. It ispracticed possible by that remote some oraltribes traditional [27,28]. It medical is possible knowledge that some may oral not betraditional reported medical and therefore knowledge not captured may not in be this reported review. an Ind thistherefore current not study, captured we collected in this review. and reviewed In this 185current epiphytic study, medicinal we collected plants and reported reviewed in the185 literature,epiphytic coveringmedicinal ethnomedicinal plants reported uses in the of epiphytes,literature, theircovering phytochemical ethnomedicinal studies uses and of the epiphytes, pharmacological their phytochemical activities. The studies data collection and the approachpharmacological used is presentedactivities. The in Figure data 1coll. ection approach used is presented in Figure 1. Figure 1. Schematic data collection approach. 2. Ethnopharmacological Information of Vascular EpiphyticEpiphytic MedicinalMedicinal PlantsPlants 2.1. Vascular Epiphytic Medicinal Plant SpeciesSpecies Distribution within PlantPlant FamiliesFamilies InIn thisthis componentcomponent of the study, wewe collatedcollated andand analysedanalysed 185185 ofof thethe medicinallymedicinally used epiphytic plantsplants speciesspecies usingusing ethnopharmacologicalethnopharmacological information.information. This This data data (Table (Table 11)) includesincludes thethe namename ofof species, plant family, areasareas wherewhere thethe epiphytesepiphytes areare usedused inin traditionaltraditional medicines,medicines, part(s)part(s) of the plant being used in medication,medication, how thethe medicinemedicine waswas prepared,prepared, andand indications.indications. Of the 185 medicinally used epiphytes,epiphytes, 53 53 species species were were ferns ferns (mostly (mostly polipodiaceae), polipodiaceae), with with 132 132 species species belonging belonging