Plants produce a variety of different chemicals throughout the course of their growth. Some of these compounds, known as secondary metabolites, are beneficial to human health. They have a wide variety of uses, including reducing inflammation, treating diabetes, reducing cancer risk, preventing cardiovascular disease, and some have antimicrobial effects [1]. The production of pharmaceutical drugs relies on many of these chemicals. Up to 60% of anti-infectious or anti-tumour drugs available are sourced from nature [2], and approximately 50% of modern pharmaceuticals overall are natural [3]. Currently, there are around 70,000 different species of plants used by both modern and traditional medicinal systems globally [4]. These plants, known as medicinal plants, have been used for thousands of years to treat health problems. In traditional Chinese medicine (TCM), for example, 80% of medicines are sourced from plants [5]. Traditional medicines are of particular importance in rural areas as up to 90% of the world’s rural population use traditional medicine, due to limited access to modern medical facilities [6]. In China, 40% of people rely exclusively on traditional medicines, while in Africa, the proportion is even greater at 80% [7]. Therefore, maintaining the availability of this valuable source of medicinal treatments is of great importance.

However, the increasing interest in medicinal plants also has negative consequences. A number of medicinal plants are listed as endangered species, and the overharvesting of them in the wild puts them at greater threat of extinction [5]. In addition, purveyors of medicinal plants often, intentionally or unintentionally, sell plants that are incorrectly labelled, and samples vary in their secondary metabolite content or are contaminated with heavy metals [8]. The use of incorrect species in herbal medicines could result in an ineffective medicine or even adverse effects. Such instances have occurred where substitution, misidentification, and contamination have resulted in severe side effects and had the potential to cause fatalities [9]. Consequently, it is key that the environmental impact of using medicinal plants is reduced and that the safety and quality of medicinal material is maintained.

To ensure a stable supply of medicinal plants, efforts to cultivate them have been made. In China, around 200 species of medicinal herbs are cultivated on over 9.3 million hectares of land [10]. Similarly, research into the cultivation of Chinese medicinal plants has been conducted in Germany, and a selection of species have reached commercial production [11]. However, there are also disadvantages to cultivating medicinal plants in the field. The concentrations of secondary metabolites present in wild populations are often higher due to the environmental stresses and competitive pressure of other species, while their slower growth rates also result in the increased accumulation of active ingredients ^[12][13][12,13]. For example, in a review of studies examining the cultivation of Hypericum perforatum L., Bruni and Sacchetti [14] observed that cultivation studies conducted in different countries reported hypericin, pseudohypericin, and hyperforin concentrations that varied widely. Similarly, differences in the salidroside yield of Rhodiola sachalinensis Boriss. (synonymous of Rhodiola rosea L.) roots were observed in response to soil characteristics, such as organic matter, nitrogen, phosphorous, and potassium content, as well as pH [15]. Additionally, seasonal variations in temperature and moisture have also been attributed to differences in the levels of phenolic compounds and saponins in Tulbaghia violacea Harv., Hypoxis hemerocallidea Fisch. & C.A.Mey., Drimia robusta Baker (synonymous of Drimia elata Jacq. ex Willd.), and Merwilla plumbea (Lindl.) Speta plants [16]. Continuous cropping of some species can also result in declining yields over time. This has been observed in Panax ginseng C.A.Mey., whose yields decline due to the proliferation of soilborne disease attributed to the accumulation of root exudates [17]. Hence, reliable methods to improve the secondary metabolite content in cultivated plant material are required.

One potential solution to this is the hydroponic cultivation of medicinal plants. Hydroponics utilises liquid media as the source of micro- and macronutrients that plants require for growth rather than the soil used in traditional systems [18]. There are a number of different systems and techniques used that fall into the category of “hydroponics”. Hydroponic techniques have been divided into two categories: solution culture and media culture, and their differences are outlined as follows.

In solution culture, the roots of plants are placed directly into liquid. Solution culture can be further subdivided into circulating and non-circulating systems. In circulating systems, nutrient solution is pumped from a reservoir into a tank, which then flows back into the reservoir. The nutrient film technique (NFT) utilises a tank on a slope which allows a shallow flow of water over the roots of the plant [19]. Contrastingly, in the deep flow technique (DFT), the tray is filled with solution and the roots are completely submerged [20]. Non-circulating systems are not pumped from a reservoir, and the nutrient solution simply sits within the culture tank and is then replaced when the nutrient concentration is inadequate or the pH or electrical conductivity (EC) are unsuitable. Examples of non-circulating systems include the root dipping technique (RDT), floating technique (FT) and capillary action technique. The root dipping technique uses plants suspended over nutrient solution while only the bottom portion of the roots are within the nutrient solution, while the floating technique sees the roots fully submerged [21], analogous to NFT and DFT, respectively. When the capillary action technique is used, nutrient solution is provided either via placing the pot into a very shallow container, where the solution then makes its way through the media by capillary action, or is transported from a reservoir to the media via wicks [22]. Finally, the ebb and flow technique is similar to DFT, but the nutrient solution is periodically drained from the culture tray and then re-added [23].

Solid media culture differs from solution culture in that plants are fully supported by a solid substrate to which nutrient solution is then applied either by surface or sub-surface fertigation. The hanging bag technique involves the hanging of around one-metre-long, media-filled polythene bags above a trough or channel. Plants in net pots are placed into holes cut into the sides of the bags. Nutrient solution is pumped from a reservoir into the top of the bags, where it then makes its way through the media, drips into the trough, and is then returned to the reservoir [24]. When the grow bag technique is used, polythene bags containing media are placed on the ground. Small holes are cut into the bag, and seedlings or seeds are then placed inside. Nutrient solution is then fed along pipes to each plant [19]. The pot technique is similar to the grow bag technique, except that plants are placed within individual pots filled with media and individually fertigated [25]. Lastly, in the trench/trough technique, trenches dug into the ground, or troughs created above ground, are lined with a waterproof material and filled with inert media. Plants are then placed in the trough at intervals and are fed nutrient solution via drip irrigation [20]. Sometimes a drainage pipe is placed at the bottom to allow excess solution to drain from the soil.

When compared with soil cultivation, there is contradictory evidence as to whether hydroponic cultivation increases the growth and secondary metabolite concentration of medicinal plants. For example, Yoshimatsu [26] observed an increase in both biomass accumulation and glycyrrhizin content of Glycyrrhiza uralensis Fisch. in hydroponics, Surendran et al. [27] recorded that the Mentha spicata L. yield, organic acid concentration, and antioxidant content were higher in hydroponically grown plants, and Duan et al. [28] found that Trichosanthes kirilowii Maxim. had greater plant height and number of leaves per plant in hydroponics, as well as a 100% seedling survival rate compared with an 87% survival rate in soil. Conversely, Afreen et al. [29] found that hydroponic cultivation resulted in a reduction of root and shoot growth of G. uralensis, while Souret and Weathers [30] observed a lower increase in fresh weight in Crocus sativus L. when it was grown in hydroponics. Similarly, Maggini et al. [31] found that the echinacoside content of hydroponically grown Echinacea angustifolia DC. was below the 1% standard required by the European Pharmacopeia, and Strzemski et al. [32] remarked that cultivation of Carlina acaulis L. in hydroponics resulted in lower carlina oxide content than when it was grown in soil. When maximising the yield and medicinal content of hydroponically grown plants is considered, the selection of hydroponic system is an important factor. Hayden [33] compared the cultivation of various medicinal plants in three different systems: NFT, ebb and flow, and aeroponics (where nutrients are provided from an atomised nutrient solution). It was found that the plants responded differently to each system, allocating resources to different parts of the plant, but that no system was specifically suited to cultivating rhizomes. Facilitating the cultivation of different plant organs is important as secondary metabolites are often concentrated within specific tissues of the plant [34]. It is therefore important to select a system suited to cultivating the specific part of the plant that is desired. This is exemplified by Afreen et al. [29], who speculated that G. uralensis grew poorly in a DFT system due to leaching of secondary metabolites into the nutrient solution. Oppositely, Yoshimatsu [26] had great success in cultivating the same plant in an NFT system, producing rhizomes with a high content of medicinal compounds. As a consequence, when cultivating medicinal plants, the hydroponic system should be carefully considered in relation to the part of the plant that is desired.

Publications on the topic of hydroponics are widespread. In a review of hydroponic research trends, Erere et al. [35] recorded a total of 2013 scholarly publications on the topic of hydroponics between 2008 and 2018. However, less than 5% (99) of publications were related to the topic of medicine. In addition, of the 207 publications not written in English, 131 (6.5% of the total studies) were written in Chinese, which makes them difficult to access for a large number of researchers. Examination of these studies may reveal insights into hydroponic medicinal plant cultivation that are seldom explored in the wider literature.

2. Hydroponic Cultivation of Medicinal Herbs

Leafy green vegetables are among the most commonly cultivated plants in hydroponic systems. Lettuce (Lactuca sativa L.) has been cultivated using DFT [36], NFT [37], and pot technique [37], while spinach (Spinacia oleracea L.) has been grown in a floating system [38] but has been said to grow more effectively in solid-substrate systems than liquid culture [39]. Additionally, NFT [40] and capillary technique [41] have been used to cultivate pak choi (Brassica rapa subsp. chinensis (L.) Hanelt). Production of these leafy vegetables is conducted on a commercial scale in a number of different countries [42], and the techniques used may be applicable to medicinal herbs. Indeed, there is an overlap between herbal plants and food plants, with many of them being used as condiments [20] or as “functional foods” [43]. Most medicinal plants that are cultivated hydroponically are those where the aerial parts of the plants are used, typically the leaves and stems [44]. They are used in a variety of ways: they can be brewed into tea, applied topically, dried and powdered, and eaten fresh or cooked in food. Additionally, pharmaceutical companies may obtain active compounds by extracting and concentrating secondary metabolites directly from the raw plant material [45]. Examples of studies hydroponically cultivating plants where the leaves and stems of plants are used medicinally are shown in Table 1. Similar to the cultivation of leafy vegetables, the most commonly used technique among studies growing medicinal plants is FT. This system is effective for the cultivation of plants that have shorter production times, as this system is prone to disease [101]. Mentha species ^[27][99][27,99], Ocimum basilicum L. ^[31][88][31,88], Agastache rugosa Kuntze ^{[46][47][48][49][50]}[46,47,48,49,50], and Urtica dioica L. [84] only require around one month from transplant to harvest, while Artemesia vulgaris L. and Stellaria media (L.) Vill. can be harvested after three months [60]. As there is no reservoir in FT, when the nutrient solution is depleted the culture container must be directly replenished. This is required on around a weekly basis ^[60][63][70][60,63,70]. The popularity of FT is likely due to the studies focusing on the effects of controlled environments on plant physiology, rather than developing techniques for commercial cultivation. Many of the studies aimed to test the response of the plants to different environmental conditions such as salt stress ^{[66][72][74][81]}[66,72,74,81], plant elicitors ^[64][72][82][64,72,82], endophytic fungi [71], heavy metal exposure [76], nitrogen enrichment [67], and macroelement omission [77]. Responses to these factors may be observed after only a few weeks of exposure, so cultivating plants to maturity may not be required. This leaves room for studies to examine the hydroponic culture of plants that take longer to grow. This is particularly important for the tree species studied—Camptotheca acuminata Decne. [67], Ilex purpurea Hassk. (now called Ilex chinensis Sims) [74], and Platycladus orientalis (L.) Franco ^[81][82][83][81,82,83]—which may be better cultivated in other hydroponic systems. While liquid culture appears to be more widely used for small leafy plants, medicinal trees and shrubs used for their leaves are hydroponically cultured using solid media systems. This is because taller plants require a solid substrate to support their weight [21]. Additionally, the basal area of the stem needs to be kept dry to prevent rot [87]. Young Moringa oleifera Lam. trees cultivated in grow bags filled with sand and coir at a 3:1 ratio and fertigated with nutrient solution had greater secondary metabolite content when compared with those grown in the field [91]. Likewise, the fresh weight and leaf number of Aloysia citrodora Paláu grown in pots containing a 3:1 mixture of perlite and sand supplied with nutrient solution were also greater than those of their soil-grown counterparts [92]. The selection of sand as a significant component of the culture medium for both experiments suggests that adequate drainage is important for larger plants. These systems may be extended for use in cultivating other medicinal trees. In particular, the grow bag system used for the cultivation of M. oleifera ^[90][91][90,91] shows promise due to its simple design. Studies focused on commercial cultivation use a variety of techniques. One particular focus is on the use of plant factories with artificial lighting (PFALs). The aim of PFALs is to optimise environmental conditions to maximise growth and phytonutrient content of high-value plants like vegetables and medicinal plants [102]. A series of studies on the cultivation of A. rugosa were conducted with the intention of optimising environmental conditions for commercial production in a PFAL ^{[46][47][48][49][50]}[46,47,48,49,50] using DFT. Similarly, Bafort et al. [53] also used DFT in determining optimum growth conditions and assessing the economic viability of producing Euphorbia peplus L. in a modified shipping container analogous to a PFAL. Two different hydroponic techniques—NFT and ebb and flow—were compared by Hayden et al. [33] for the purposes of developing commercial cultivation. They found that Mentha × piperita L. and Nepeta cataria L. grew well in the ebb and flow system, while both systems were less effective than aeroponics for a variety of species. The use of FT has also been proposed for the commercial production of O. basilicum [31], as well as A. vulgaris and S. media [60], as it has low start-up costs and is cheap to run [45]. Cannabis sativa L. has been extensively studied due to its popularity as a recreational and medicinal drug. In addition, its high economic value means that cannabis cultivation is at the forefront of innovation with regards to the adoption of modern commercial production techniques for plants [103]. It has been cultivated in numerous hydroponic systems, but ebb and flow and NFT are among the most widely used and high-yielding systems [51]. These factors make studies on C. sativa cultivation valuable resources for determining the best practices for growing leafy medicinal plants.