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Abstract
Trema orientale (L.) Blume is an important medicinal plant with multiple applications for treating several disease conditions. This study compiled published data on botanical, traditional uses, phytochemistry, pharmacology, and antimicrobials, coupled with discussing the conservation and domestication potential of T. orientale. Data were sourced from databases such as Google Scholar, PubMed, Scopus, Elsevier Plants of the World Online (Kew Science), Global Biodiversity Information Facility (GBIF), and World Flora Online (WFO), using key search terms: Trema orientale or orientalis, phytochemistry pharmacology, taxonomy, and domestication with Boolean operators to include and exclude articles for the review. The review indicated that molecular studies have shown that T. orientale is closely related to a sister group of Cannabis through plastome phylogenetic evidence which accounts for its transfer from Ulmaceae to the Cannabaceae family. T. orientale is distributed across several African countries and has recently been assessed as the Least Concern by the IUCN Red List of Threatened Species. Nevertheless, deforestation continues to pose an extinction risk to their population. Currently, 31 compounds have been isolated from different parts of T. orientale justifying many traditional uses accredited to it. T. orientale is considered a dose-dependent safe remedy for the treatment of infectious diseases, cancer, cardiovascular diseases and other disease conditions ascribed to it except for its continuous application. This review underscores the domestication potential of T. orientale including evidence of molecular markers, soil seed banks, and promising outcomes of germination experimentations. This, therefore, presents significant gains toward sustainable utilization of Trema orientale.
1. Introduction
The use of plants as medicine has been the backbone of mankind’s existence on Earth. This is particularly important in most tropical countries where their rich plant biodiversity affords them the luxury to select from the plethora of plant resources with therapeutic potential. In developing countries, the use of plant medicine is the primary medical remedy for many people especially, among the rural population for treating and managing various disease conditions [1]. About 80 % of the world’s population depends on herbal medicine because it is less costly, readily and easily accessible to consumers [2].
The application of plant medicine as primary healthcare has been heightened in the 21st century [3]. It is now more popular among the elite who hitherto doubted the efficacy and safety of plant medicine. This could be attributed to the integration of orthodox synthesis of drugs into the plant medicine production system [4]. As a result, many chemical constituents with multiple medicinal potentials have been isolated from plants, confirming the medicinal potency of most plants [[5], [6], [7]]. In addition, the availability of in-vitro, ex-vivo [[8], [9], [10], [11]], and clinical trials of some plants to ascertain their efficacies have been studied [12,13]. The recognition by the World Health Organization (WHO) of the effectiveness of herbal remedies and the subsequent support to countries to develop and improve herbal medicine has also assuaged fears and myths associated with the use of plant medicine [14]. Literature has reported on the medicinal potency of several plants for treating common ailments like cancer, malaria, fever, asthma, and diarrhoea [[15], [16], [17], [18], [19]].
Trema orientale (L.) Blume. is an evergreen tree in the family Cannabaceae. Some of its common names include charcoal tree, gunpowder tree, pigeon wood, hop out, Indian charcoal tree, and Indian nettle tree. It has a widespread distribution across several zones, particularly in the tropics, and some temperate zones. It is indicated that almost all parts of the plants have some medicinal application [20]; stem bark for the treatment of malaria [21], leaves are used as dewormers for hookworms and roundworms [22], inflammatory and respiratory diseases [23]. It thrives well in the humid tropics and it is mostly sourced from the wild.
Forest biodiversity is an important source of plant resources [24]. However, land use changes particularly the conversion of rich biodiversity areas for farming, physical developments, and mining with its attendant problem of climate change pose a serious extinction risk to the sustainable utilization of plants in general particularly T. orientale. For instance, Uganda reported that rapid habitat loss has exacerbated the already dwindling population sizes of T. orientale [25], although previous authors have widely reviewed the importance of T. orientale in terms of phytoconstituents [[26], [27], [28]], and mechanical and wood properties [[29], [30], [31]]. Yet, there is a dearth of review data on the botany/diversity and domestication potential of T. orientale demonstrated by literature. Thus, this review sought to highlight the botany, availability, medicinal importance, and domestication potential, in addition to the pharmacological and phytoconstituents of Trema orientale. This review exemplifies a comprehensive documentation of available literature on T. orientale in contemporary times.
2. Methodology
Information for this review was gleaned from Google Scholar, Research Gate, PubMed, Science Direct, Elsevier, Taylor and Francis and other online resources such as the POWO and WFO. The keywords used in the search engines are Trema, taxonomy, phytochemistry, biological activity, traditional uses and domestication of Trema orientalis. These keywords were used together with other terms relating to the subject of the review and were used interchangeably during the search process. For Google Scholar, Google, Research Gate, Scopus, Elsevier, Taylor and Francis and PubMed we only searched for peer-reviewed articles published between 2000 and 2022 with the keyword “Trema. From our analysis of the search results, it was realized that most of the articles reported on the wood/mechanical properties of T. orientale. The next action was to search with Boolean operators (AND, OR or AND NOT, +) to combine or exclude the key terms that directly relate to the purpose of this review in all the databases searched. Thus, we used the terms ‘taxonomy’, ‘phytochemistry’, ‘biological activity, ‘traditional uses’, and ‘domestication potential’ of the Genus Trema in the searches (Table 1). This excluded some of the documents resulting in articles mainly reporting on the phytochemistry, and biological/pharmacological activities of the Genus Trema with little information on the botanical and conservation aspects. Further screening with specific emphasis on Trema orientale using the same keywords excluded some of the articles. We analyzed each of the remaining articles and key points relating to phytochemistry, and biological activity summarized. We, therefore, resorted to the POWO, WFO Plant List, and GBIF databases to analyze the taxonomic data using these keywords ‘botanical description’; ‘traditional uses’; and ‘domestication of T. orientale’ together with the Boolean operators (Table 1). All documents directly relating to the inclusion criteria were analyzed and included in the review.
Table 1
Trema OR Trema orientalis OR Trema orientale |
---|
AND |
Phytochemical OR Phytoconstituents + Pharmacology OR Biological activity |
AND |
Taxonomy OR Botany OR Botanical description |
AND/OR |
Domestication OR Cultivation |
Economic importance OR Traditional uses |
3. Taxonomy of Trema orientale
Trema orientale, formerly Trema orientalis in the Kingdom Plantae falls under the taxonomic rank of vascular plants Phylum Tracheophyta and a subdivision Spermatophytina (spermatophytes, seed plants, or phanérogames). It is also categorized under the class Magnoliopsida and associated with the order Rosales. Nested within the Rosales are four families, which in the past have been variously delimited in an order of Urticales. The Urticales informally referred to as Urticalean Rosids, comprise Ulmaceae, Moraceae, Urticaceae and Cannabaceae. These families are grouped based on their shared characteristics and they include taxa with small, unisexual and wind-pollinated flowers [32,33]. It is worth noting that, the distinctive characteristics of these plant families have led to their worldwide classification as culturally and economically important plants. T. orientale previously belonged to Ulmaceae but is currently an accepted species in Cannabaceae. Molecular studies have shown that T. orientale is closely related to a sister group of Cannabis through plastome phylogenetic evidence [34]. Further knowledge on the uses of some species, particularly, in the genera Cannabis L., Celtis L., Trema Lour. and Humulus L. has been reported in previous studies [35,36]. They contribute immensely to addressing critical challenges facing humanity such as healthcare, poverty and food security. For instance, Cannabis sativa is used as a bast fiber plant; hemp, and the euphoric medicinal plant; marijuana [33,37].
The family Cannabaceae consists of 9 genera and 109 accepted species (https://powo.science.kew.org/; accessed on January 25, 2023). The family is predominantly of trees and shrubs but is also represented by herbs and vines. They are dioecious or sometimes monoecious, leaves are alternate, opposite, compound or sometimes simple. Other studies reported that Cannabaceae is currently recognized as a distinct family consisting of Cannabis L. and Humulus L. which was initially separated from the family Moraceae by Rendle [34,37,38]. Molecular studies on Cannabaceae remain unresolved because of limited taxon and character sampling, however, some morphological characters can be used for their identification [39].
3.1. Distribution, habitat and description Trema orientale (L.) Blume
T. orientale, is a large shrub or medium-sized tree found in the tropical and sub-tropical wet regions. It has an extensive root system that enables it to survive long periods of drought [40]. The height varies depending on the location and climatic conditions. In general, it prefers sites that experience high rainfall and the form it takes is dependent on the individuals’ access to water, thus, it can grow from 8 ft to 20 ft in height [41,42]. It has a short basally swollen bole, heavy branching rounded to spreading crown and slender branchlets covered with white velvety hairs (Fig. 1c). The stem bark is grey or dark brown, smooth, and marked with parallel longitudinal lines and corky spots (Fig. 1d). It produces a creamy-white to light yellow, fibrous, bright green latex immediately beneath the bark when slashed [23,43]. The leaves are long, simple, alternate, stipulate along drooping branches about 14 cm long, and the stipules are three-nerved at the base, with unequal size (Fig. 1b). The leaf surface is papery, glabrous, rough to the touch and dull at the adaxial surface with short grey hairs below. The edges are finely toothed all around with an unequal-sided blade [43]. Leaf margins are closely serrated from near the base, whereas the juvenile leaves are rough and hairy, up to (15 × 9 cm) but become smooth when they mature. The plant is pollinated by bees and flowers from December to February, producing cymes about 5–10 mm long [44]. Flowers are mostly male with a few female (bisexual) flowers at the top; small, inconspicuous and greenish-cream. Bracts are 1 mm. long, triangular; pedicels short or absent. The fruits are small and round drupes and can either be green or dark purple but turn black when ripe [44] (Fig. 1a).
T. orientale is a widely distributed tree species that remains abundant despite deforestation in some parts of its habitat. The native habitat of this species is tropical and subtropical regions. It covers three continents and encompasses 65 countries; particularly Africa and continental Asia [23] (Fig. 2). It has been introduced to Hawaii, Mauritius and Reunion. The species is not common across its whole range but it has a large population. It is also common in secondary forests and grows well in both heavy and light soils, it can also be established on flood-damaged river banks [40,46]. This species has most recently been assessed for the IUCN Red List of Threatened Species in 2017 and is listed as Least Concern. The estimated Area of Occupancy (AOO) is 1560.000 km2 and the Estimated Extent of Occurrence (EOO) is 26,493,751.440 km2 [45,46]. T. orientale has been referred to differently in different locations (Table 2).
Table 2
Location/Country | Common/Vernacular names |
---|---|
Ghana | Osesea (Twi); Wadzawadza (Ewe) |
Nigeria | Afere, Afefe, Anyinyin (Yoruba); Telemukwu (Igbo), Ehun-ogo (Bini) |
Angola | Kipesi (Umbundu); Mugudisisola (Kimbundu); Nsengue-nsengue (Kikongo); tjimonomono (Cokwe) |
Kenya | Mzunguzungu (Taita) |
3.2. Traditional medicinal uses
Almost all the parts of T. orientale have traditionally been used for the treatment of several diseases all over the world, especially in Africa. The leaves have reportedly been used for the treatment of coughs and sore throats while the bark is used to make cough syrup. Other reported uses include remedies for asthma, bronchitis, gonorrhoea, malaria, yellow fever, toothaches, and intestinal worms [47]. Sometimes, the leaves and fruits are processed into infusions and taken for conditions such as bronchitis, pneumonia, and pleurisy [48]. In Ghana, the leaves only or with fruit, enrich the recipe by crushing the leaves in lemon juice for cough treatment [49]. The stems and twigs have been useful in the management and treatment of respiratory disorders, fevers, toothache, and venereal diseases in West Africa [50]. The Ghana Herbal Pharmacopeia reported on its use as a dewormer for hookworm and roundworm treatment [22]. In Nigeria, T. orientale has also been used for restoring tired muscles and aching bones [50].
4. Phytoconstituents of T. orientale
The major groups of phytochemicals present in Trema orientale are tannins, flavonoids, saponins, cardiac glycoside, phytosterols, fatty acids, carbohydrates, iridoids, xanthones and phenolic compounds [33,52,53]. Some isolated compounds from various parts of the plant and their structures are listed in Table 3 below.
Table 3
Sr. No. | Compound Name | Structure | Plant Part | Reference |
---|---|---|---|---|
1. | (−) -ampelopsin F | Stem | [26] | |
2. | (−)-Epicatechin | Stem | [26,51] | |
3. | (+) -Catechin | Stem | [26] | |
4. | (+) -Syringaresinol | Stem | [26] | |
5. | (3R*,3aR*,4R*,5S*)-6-OR-arabinopyranosyl-8-hydroxy-3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)-5-(3,5-dihydroxyphenyl)-3,3adihydrocyclopenta [1,2,3-de] isobenzopyran-1-one | Root Bark | [52] | |
6. | (9S*,10S*)-3-[7-(3,10-dihydroxy-9-hydroxymethyl-2,5- dimethoxy)-9,10 -dihydrophenanthrenyl] propenal |
Stem Bark | [52] | |
7. | (9S*,10S*)-3- [7-(5-O– ß -glucopyranosyl-10-hydroxy-9-hydroxymethyl-2,6-dimethoxy)-9,10-dihydrophenanthrenyl] propenal | Stem Bark | [52] | |
8. | 1-octacosanyl acetate | Stem | [53] | |
9. | 1-O-glucosyldecussatin | Stem Bark | [54] | |
10. | 1-O-primeverosyl-decussatine | Stem Bark | [55] | |
11. | 2a, 3a, 23-trihydroxyurs-12-en-28-oic acid | Root Bark | [56,57] | |
12. | 3,4-dihydroxybenzoic acid | Root Bark | [58] | |
13. | 3,5-dimethoxy-4-hydroxyphenyl -1-O-β-D-glucoside | Stem | [26] | |
14. | 3-O-ß-glucopyranosyl-ß-sitosterol | Root Bark | [59] | |
15. | 3ß-dihydroxyurs-12-en-28-oic acid | Root Bark | [56] | |
16. | Decussatin | Stem Bark | [60] | |
17. | Episimiarenol | Stem | [61] | |
18. | Hexacosanoic acid | Root Bark | [62] | |
19. | Lupeol | Stem Bark | [63] | |
20. | Methylswertianin | Stem Bark | [64] | |
21. | N-(trans-ρ-coumaroyl) octopamin | Stem | [26] | |
22. | N-(trans-ρ-coumaroyl) tyramine | Stem | [26] | |
23. | Tetracosanoic acid | Stem | [53] | |
24. | Scopoletin | Stem Bark | [65] | |
25. | Simiarenol | Stem | [61] | |
26. | Simiarenone | Root Bark | [58] | |
27. | β-sitosterol | Root Bark | [59] | |
28. | Sweroside | Stem Bark | [66,67] | |
29. | Trans-4-hydroxy-cinnamic acid | Stem | [26] | |
30. | Trematol | Stem | [53] | |
31. | ρ-hydroxybenzoic acid | Stem Bark | [63] |
5. Pharmacological activities/studies
There have been several studies over the years on Trema orientale including in-vitro and in-vivo studies using different extraction methods and/or part of the plant to establish its pharmacological effects. These reports include anti-inflammatory, antimicrobial, antidiabetic, antioxidant, and antidepressant activities among others. The main pharmacological studies on T. orientale are abridged and highlighted under this topic [23,33].
5.1. Anthelmintic activity
The antiparasitic effects of crude extract of Trema. orientale bark and wood with hexane, ethanol and water against Caenorhabditis elegans have been reported. The research confirmed that a concentration higher than 1 mg/ml of the extracts has inhibitory activity against C. elegans within the first 2 h of exposure and lethal activity after 7 days of exposure [32]. Similarly, an in-vitro anthelmintic evaluation of 70 % ethanolic leaf extract of T. orientalis on nematode larvae of sheep and goats was studied. To achieve the nematode larval mortality, larvae were isolated and counted from the faeces of the ruminants using the Baermann set-up/technique and exposed to different concentrations of the extracts. The results showed that the concentrations had anthelmintic activity against nematode larvae [68].
5.2. Cardioprotective activity
An in-vivo antihypertensive effect of ethanol extracts of Trema orientale was conducted on male Wistar albino rats. Crude ethanolic extract of the plant was obtained using its leafy stem. N(G)-Nitro-l-Arginine-Methyl Ester (l-NAME) was administered to the rats two weeks before the commencement of the treatment, to induce hypertension. The animals were monitored for four weeks during the treatment period and the blood pressure (BP) of the experimental animals was recorded by the use of a non-invasive BP system. At 500 mg/kg body weight (bw), T. orientale reduced mean arterial pressure from 154.8 ± 7.84 to 103 ± 5.6 mmHg [69]. Likewise, it is indicated that T. orientale is a potential antihyperlipidemic agent, reducing the risks of cardiovascular diseases. This study was carried out in Wistar albino rats by inducing the rat models with 25 % fructose for 15 days and Triton, treating them with ethanolic leaf extract of the plant. Blood samples were then collected from the animals to conduct biochemical analysis including but not limited to Total Cholesterol, High-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol. The biochemical tests and histopathology studies revealed that the plant has hypolipidemic activity [70].
5.3. Anticancer activity
A recent study has been conducted to assess the anticancer effect of T. orientale aerial parts using methanol for the extraction process. In-vitro cytotoxicity assay was carried out in eight human cell lines and normal fibroblast cells, thus HCT116 (colorectal carcinoma cell line), A2780 (ovary adenocarcinoma), MRC5 (normal fetal lung fibroblast), MCF7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HepG22 (liver cancer cell line), TK10 (kidney renal cell adenocarcinoma), MDA231 (breast cancer cell line), and PC3 (prostate cancer cell line). It is indicated that the leaf extract was highly toxic to HCT116 cell lines at 2.256 ± 0.85 μg/mL, as compared to the other parts and therefore, a clonogenicity assay was conducted to determine the growth inhibitory effects of the plant. The results showed that HCT116 cells significantly declined, about 98 % at 7.5 μg/mL after fourteen days of incubation and exhibited the strongest clonogenic activity [71]. Similarly, Kabir et al. [72] studied the anticancer potential of T. orientale methanolic leaf extracts in Swiss albino mice against Ehrlich ascites carcinoma (EAC). The animals were transplanted with EAC and treated for six days with the crude extract, intraperitoneal EAC cells were then collected, harvested and counted by hemocytometer. The LD50 of the extract was 3120.650 mg/kg bw, proving its safety at a dosage of as high as 800 mg/kg bw. The in-vivo evaluation at 400 mg/kg bw showed that the extract inhibited nearly 59 % growth of tumour cells in comparison with the control group, with considerable apoptotic characteristics. To validate this outcome, an in-vitro test using 3- [4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was also conducted. The MTT assay of the plant extract was cytotoxic with an IC50 value of 29.952 ± 1.816 μg/mL, demonstrating that the plant has an anti-cancer effect.
5.4. Antioxidant activity
The antioxidant activity of the leafy stem of T. orientale with its ethanolic crude extract using 2, 2-diphenyl-1-picryl-hydrazyl (DPPH), Ferric reducing capacity (FRC), superoxide anion and hydrogen peroxide (H2O2) assays was studied by Madjid et al. [73]. The FRC assay was established to have the best activity with 6007.8 ± 175.57 μmol AAE g-1. The scavenging activities of H2O2 and superoxide anion resulted in between 88.52 ± 0.68 % to 91.33 ± 4.01 % while DPPH also showed promising inhibitory activity of 83.86 ± 1.88 and 99.46 ± 0.38 when compared to ascorbic acid. Likewise, methanolic extracts of T. orientale leaf, root, stem and aerial parts were evaluated for their antioxidant activity using a DPPH assay [74]. However, no scavenging activity was noted for the aerial parts while the IC50 value of the leaf, root, stem extracts and ascorbic acid were 13.1 ± 0.2, 7.4 ± 0.2, 6.4 ± 0.2 and 1.01 ± 0.4 μg/mL, respectively. Following the same approach using DPPH assay, Saleh et al. [75] determined the antioxidant activity of T. orientale ethanolic extract of the leaves. The IC50 of the free radical scavenging activity was 9.27 μg/mL, which proves the antioxidant potential of the plant. The same analysis was conducted for its aqueous extract but did not show antioxidant activity. Recently, Al-Robai et al. [71] used DPPH and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays to establish the antioxidant activities of methanolic extract of T. orientale aerial parts using ascorbic acid, propyl gallate, and Trolox as positive controls. All the extracts exhibited free radical scavenging activities in both methods. The DPPH method recorded a scavenging activity of 79.6 % while ABTS recorded 84.43 % for the leaf extract; ascorbic acid, propyl gallate, and Trolox as 92.86 %, 82.30 and 78.72 %, respectively in the ABTS method. This shows that the plant extract was more effective than propyl gallate, and Trolox. Although there was a significant difference between the DPPH and ABTS assay results, the values indicated that the leaves had the strongest activity, followed by bark, twigs and fruits in that order.
5.5. Antimicrobial activity
A study in India using 15 isolates of Staphylococcus aureus indicated that acetone extract of T. orientalis inhibits the growth of the organism with a MIC value of 3.7 mg/ml and biofilm inhibitory concentration value of 2.7 mg/mL [76]. It is also indicated that methanolic extract from T. orientale leaves has an antibacterial effect against some Gram-positive and Gram-negative bacteria. The mean zones of inhibition for Bacillus subtilis, Micrococcus luteus, Escherichia coli, Salmonella enterica serotype Typhi, Shigella dysenteriae, Klebsiella pneumoniae and Pseudomonas vulgaris were 11.20 ± 0.81 mm, with S. Typhi and S. dysenteriae being more susceptible. However, this study showed that Xanthomonas campestris and Pseudomonas denitrificans were resistant to the extract [77].
A study was conducted to understand the inhibitory activity of granules against Salmonella spp. using wet granulated granules formulated from methanolic leaf extract of T. orientalis as the active ingredient. Excipients used in the formulation included sucrose, polyvinylpyrrolidone, sorbitol, lactose and water and with the concentrations of 0.25 mg/200g, 12.5 mg/200g and 6.5 mg/200g of the granules, to which the organism was susceptible to all three concentrations [78]. This finding is consistent with a study by Rahman et al. [77] which was conducted on S. Typhi. Similarly, Napiroon et al. [37] sampled T. orientalis from various regions of Thailand to make lipophilic extracts and fractions to evaluate the presence of cannabinoids and their antimicrobial activities. The extracts inhibited Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii with minimum inhibitory concentrations (MICs) ranging between 31.25 and 125 μg/mL. Likewise, the antimicrobial efficacy of T. orientalis aerial parts was assessed using methanolic crude extracts of the leaves, fruits, bark and twigs against two Gram-positive, and two Gram-negative bacteria and opportunistic yeast. Using E. coli, K. pneumoniae, S. aureus, Enterococcus faecalis and Candida albicans as the test organisms, the results indicated inhibitory activity of the leaves against only C. albicans while the bacteria were resistant to other parts of the plant [71]. This finding is however contradicting other studies which reported that S. aureus was susceptible to the plant. This could however be attributed to the different extraction methods used [37,77].
The susceptibility patterns of S. aureus, P. aeruginosa, E. coli, S. Typhi, S. dysenteriae, Streptococcus faecalis, Proteus mirabilis, Haemolytic Streptococcus viridian, Aspergillus niger, C. albicans and Aspergillus flavus to methanol and petroleum ether extracts of T. orientale leaves were also investigated [79]. Salmonella Typhi was the most susceptible organism against both extracts, confirming other studies [77,78]. Nevertheless, S. aureus and S. dysenteriae exhibited resistance to the extracts which are different from other reports [37,76,77] but confirmed Al-Robai et al. [71] findings. These inconsistencies could be attributed to differences in the inoculum size, extract concentrations, methods used and the geographical area of the plant as described by Eloff [80].
6. Safety and toxicity studies
It is indicated that the methanolic leaf extract of T. orientalis is less toxic to cells with LC50 of 170.2 μg/mL when compared to vincristine sulphate standard which has LC50 of 2.5 μg/mL using the brine shrimp lethality bioassay [77].
In-vivo research was undertaken to explore how methanolic leaf extract of T. orientale affects the liver of Wistar rats. Cadmium chloride was administered to the animals, followed by T. orientale extract of dosages 100 and 200 mg/kg bw and observed for 21 days. Blood and tissue samples were collected from the rats for biochemical tests and histopathology studies. The total protein and alanine aminotransferase (ALT) in rats treated with cadmium chloride plus the extract was not significantly different from the control group. Histology studies revealed mild toxicity in the liver tissues when the extract was continuously administered raising important concerns about dosage [81].
Acute and sub-acute toxicity studies in Wistar albino rats were conducted using methanolic extract of T. orientale aerial part. Doses of 1, 2, 3, and 4 g/kg were used for the acute toxicology as animals were observed for 14 days. The animals were administered with 0.25, 0.5 and 1 g/kg bw of the extract, observed for 28 days and sacrificed for blood and tissue examinations during the sub-acute toxicity study. No death or changes in behaviour or toxicity were observed during the acute toxicity, proven the lethal dose (LD50) being greater than 2 g/kg. Alkaline phosphatase, total protein and albumin increased significantly in groups administered as with higher doses [82]. They concluded that the plant is safe at a lower concentration, and this agrees with the study [81].
In a similar study, it was established that T. orientale methanolic leaf extract doses of 100 and 200 mg/kg were toxic after continuous administration to Wistar rats. They reported an increase in haematology test parameters in rats treated with only the extract and animals that were administered with both the extract and Cadmium. The study also proved that the leaves of T. orientalis have both hematoprotective and hematopoietic properties which could support patients with anaemia [83].
7. Domestication potential
Domestication is the introduction of an organism into a new environment other than its natural habitat with conducive conditions for its survival [84]. The domestication process to a large extent focuses on the morphological and genetic assessment between a species and its existing wild relatives [85], and basically to improve its suitability and perpetual outcome of its benefits for human consumption, especially in yield, taste, cultivation practices, and storage [86]. Among all considerations, it is noted that the identification of individual species with desirable traits is the foremost in selecting species for domestication [87,88]. In addition, targeting species with improved palatability, increased productivity of harvested parts, ease of growth, and harvest on farmlands [89]. Consequently, an important task is to focus on the qualitative traits of species such as tree form, fruit shape, and sweeter pulp [90], which could result in 60 % of the progeny resembling the mother tree, especially in terms of productivity and ease of cultivation [91]. An equally important factor for improved domestication is the environment and condition of the seeds.
Studies have indicated a significant presence of T. orientale in soil seed banks in different forest ecosystems [92]. Likewise, studies by Hall & Swaine [93], also reported on the abundance of T. orientale in Ghanaian forests. In Thailand, viable seeds of T. orientale were found in soil seed banks 175 m from the mother tree [94]. Yet only a small fraction may germinate under favourable conditions due to the dormant nature of the seeds [95,96]. Though several species of birds aid in the seed dispersal of T. orientale, fleshly ripe fruits rarely germinate and mostly decay especially in storage [[97], [98], [99]]. Hence, requiring intervention to preserve and accelerate its germination process. A recent study by Nugraheni and Yuniarti [100], recommended that the optimum condition to maintain seed viability for at least one month and speed germination of T. orientale is to dry it for 24 hr, and put it in an air-tight aluminium foil container in an air condition room. Similarly, the highest growth uniformity of 74.75 % and 72 % before storage and after storage respectively was obtained by subjecting T. orientale seeds to a hydrated-dehydrated procedure [99]. Studies by Rodrigues and Rodrigues [101], indicated the potential of enhancing the seeds of T. orientale through different pre-treatment options. Among other pre-sowing treatments, the authors indicated that soaking and depulping the seeds in concentrated H2SO2 for 2 hr and 15 min respectively yielded the highest germination and healthy plantlet. The prospect of vegetative propagation of T. orientale has also been indicated in the literature. It is reported that rooted cuttings treated with 300 ppm of naphthalene acetic acid exhibited the highest percentage of germination when planted in sandy soil [102]. These outcomes significantly contribute to the sustainable propagation and utilization of T. orientale.
8. Conclusions
This review documents the traditional uses, taxonomy, domestication potential, pharmacological activities and phytoconstituents of T. orientale in a bid to highlight its medicinal importance. T. orientale forms an important component of the herbal remedy of many people in Africa due to its multiple applications. This has been attributed to its rapid decline coupled with its germination difficulties. Nonetheless, it is established that there is enormous potential to improve seed quality through molecular markers and germination trials (pre-sowing treatments). This review demonstrates the phytochemical and medical properties of T. orientale and establishes that, at safe dosages, it may be used as a potent herbal remedy for a wide range of health conditions like infectious diseases, cancer and cardiovascular diseases. Phytochemical studies show the presence of phytosterols, flavonoids, tannins, saponins, cardiac glycosides, fatty acids, and phenolic compounds as secondary metabolites. Some compounds have however been isolated from the plant and there is a need for further studies to specify the compounds accounting for these activities, with their pharmacodynamics and pharmacokinetics.
Funding statement
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
CRediT authorship contribution statement
Yaw Appau: Conceptualization, Methodology, Writing – original draft, Writing – review & editing. Paa Kwesi Gordon: Methodology, Validation, Writing – original draft, Writing – review & editing. Seyiram Kumordzie: Methodology, Writing – original draft, Writing – review & editing. Michael Odoi Kyene: Methodology, Writing – original draft, Writing – review & editing. Peter Atta-Adjei Jnr: Conceptualization, Methodology, Writing – original draft, Writing – review & editing.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.