key: cord-0072779-1d4boeyb
authors: Chukwudulue, Uche Maryann; Attah, Alfred Francis; Okoye, Festus Basden Chiedu
title: Linking phytochemistry to traditional uses and pharmacology of an underexplored genus – Psydrax: a review
date: 2022-01-04
journal: Phytochem Rev
DOI: 10.1007/s11101-021-09798-6
sha: 991fa8dbcc4e0dc822fa17714adf47ca1efd2f70
doc_id: 72779
cord_uid: 1d4boeyb

The genus Psydrax is one of the ethno-medicinally important genera of the Rubiaceae family which has only received a limited scientific attention, despite coming from a pharmacologically and phytochemically important plant family. The genus has found applications in ethnomedical management of diabetes, stomach disorders, inflammations, cardiovascular diseases, epilepsy, wounds, malaria and fever. To unveil knowledge gaps, stimulate research interest and unravel opportunities for drug discovery from the genus Psydrax, we have carried out an extensive review on its traditional applications, phytochemistry and pharmacology for the first time. Literature on these topics was obtained from Google Scholar, Pubmed and ScienceDirect journal articles published from 1788 to September, 2021. Only articles written in English were reviewed. While several species of Pysdrax used in traditional medicine have not been chemically explored for drug discovery, over a hundred secondary metabolites have so far been identified in few species of the genus, and majority of these chemotaxonomic markers are iridoids. Bioactive extracts and some isolated constituents of Psydrax species have shown various in vitro and in vivo pharmacological properties including anti-hyperglycemia, anti-inflammatory, anticonvulsant and antimicrobial, and thus, support some of the ethnomedical uses of the plants. For an evidence-informed application of the genus, Psydrax, in traditional medicine, more ethnobotanical surveys, elaborate in vivo pharmacological assays, in-depth toxicity and holistic phytochemical studies are required to fully exploit more species of the genus prior to future clinical studies. Following documented traditional uses of Psydrax species, the deliberate cultivation of medicinal plants under this genus is recommended for sustainability in medicinal plant utilization.

written in English were reviewed. While several species of Pysdrax used in traditional medicine have not been chemically explored for drug discovery, over a hundred secondary metabolites have so far been identified in few species of the genus, and majority of these chemotaxonomic markers are iridoids. Bioactive extracts and some isolated constituents of Psydrax species have shown various in vitro and in vivo pharmacological properties including anti-hyperglycemia, anti-inflammatory, anticonvulsant and antimicrobial, and thus, support some of the ethnomedical uses of the plants. For an evidenceinformed application of the genus, Psydrax, in traditional medicine, more ethnobotanical surveys, elaborate in vivo pharmacological assays, in-depth toxicity and holistic phytochemical studies are required to fully exploit more species of the genus prior to future clinical studies. Following documented traditional uses of Psydrax species, the deliberate cultivation of medicinal plants under this genus is recommended for sustainability in medicinal plant utilization.

The Rubiaceae plant family has served as an important source of bioactive compounds and ''leads'' for drug discovery and development (Buathong et al. 2019; Koehbach et al. 2013; Maldonado et al. 2017; Wijnsma and Verpoorte 1986) . While other genera within the Rubiaceae family have received considerable research attention as well as reviews on their species (Fan et al. 2020; Gibbons 2020; Heitzman et al. 2005; Kala 2015; Taher et al. 2020 ) which has stimulated further research, Psydrax genus has been underexplored scientifically; the genus has not been previously reviewed to reveal knowledge gaps and provide opportunities for further studies.

The genus name, Psydrax Gaertn., originally introduced, in 1788, by Joseph Gaertner in his book (Gaertner 1788) was abandoned until A. Richard included it in one of his papers in 1830, and was later reinstated by Bridson in 1985 (Bridson 1985 . It belongs to the Vanguerieae tribe of the Rubiaceae family and is subdivided into two subgenera, the palaeotropical subgenus Psydrax, which exists as trees, shrubs or sometimes as scandent, and the African subgenus Phallaria, which exists as lianas or scandent shrubs (Bridson 1986 (Bridson , 1985 . In this review, the common name Psydrax, would be adopted for the two subgenera, Phallaria and Psydrax. The full lineage of the genus, according to the NCBI taxonomy database, is shown in Table 1 .

While Psydrax is known to be monophyletic (Bremer 2009; Lantz and Bremer 2004) , with defined morphological characters, it still shares most of its characters with Keetia (Bridson 1985; Lantz et al. 2002; Lantz and Bremer 2004) , which is a closely related genus also transferred from Canthium) and its circumscription is somehow problematic, with species more readily added to it (Davis et al. 2007 ). However, the Southern African Canthium s. str. (the remaining part of Canthium after the reinstatement of Psydrax and Keetia) and Psydrax can be distinguished distinctively by the anatomical features of their leaves and young stems (Tilney et al. 1990 (Tilney et al. , 1988 , while Keetia can be distinguished morphologically from Psydrax by its pyrene, anther and carlyx-limb (Bridson 1986; Lantz et al. 2002) . Psydrax species go with varying synonyms which are adopted by different authors, and their number keeps increasing as new species, which are yet to be included in The Plant List database, are being discovered (Arriola and Alejandro 2013; Arriola et al. 2017; Mahyuni et al. 2019) . In 2020, a new species, P. gialaiensis, was discovered in Gia Lai Province, Southern Vietnam (Quang et al. 2020 ) and has been uploaded on the website of the World Checklist of Selected Plant Families(WCSP) alongside another new species, Psydrax lanceolatus.

As the largest and widest geographically distributed genus of Vanguerieae tribe (Lantz et al. 2002; Lantz and Bremer 2004) , Psydrax is reportedly found in three continents, Africa, Asia and Oceania. According to the WCSP (wcsp.science.kew.org), accessed on 22 September, 2021, 130 species are included in the genus, as listed with their continental distributions in Table 2 . However, two species, P. horizontale and P. hullensis, were missing in WCSP database, but were included in Tropicos and The Plant List databases, and eight names out of the 130 species' names in the WCSP database were unaccepted. Bridson and other group of researchers (Bridson 1985; Lantz et al. 2002) reported that more than thirty species of the genus are native to Africa, and these are not far from the WCSP's list of continental distribution of 54 species of the genus in different countries in Africa. Though, Psydrax is the largest genus in its tribe, some of its species are rare and at the verge of extinction (Cheek and Sonké 2004; Subashree et al. 2021) , and their decreasing population may be ascribed to their traditional uses (Arriola et al. 2017; Tabuti et al. 2009 Tabuti et al. , 2011 . Surprisingly, only about 8% of Psydrax species have been reported for their ethnomedicinal uses and pharmacological activities, with P. subcordata (DC.) Bridson having the highest coverage. In other words, close to 92% of this genus have not received scientific attention beginning from documentation of local knowledge on the genus via ethnopharmacological surveys, and the ethnomedicinal application of species within this genus in meeting primary healthcare needs. Across Africa, different parts of P. subcordata (DC.) Bridson are used in the treatment of varied health issues such as cardiovascular diseases, inflammation, stomach disorder, epilepsy, malaria and fever (Awah et al. 2012; Awantu et al. 2019; Chukwujekwu et al. 2005; Daanaa et al. 2018) . P. dicoccos, found mostly in Asia, is used in folk medicine for rheumatoid pains and asthma Neelima et al. 2011) . Psydrax species have also found applications in ethnoveterinary medicine as wound healing and antiparasitic agents, in the treatment of ectoparasites, and as piscicide in fish farming (Maroyi 2012; Mukandiwa et al. 2012a, b; Nyahangare et al. 2015; Raja et al. 2011) .

Phytochemical screening of few of the Psydrax species revealed that the major phytochemical class in these plants is the iridoid. Interestingly, iridoids have been reported to possess a number of pharmacological and biological activities, such as antimalarial, antidiabetic, antioxidant, antitumor, antibacterial, antiviral, anti-inflammatory, neuroprotective and cardioprotective effects (Ghisalberti 1998; Tundis et al. 2008) . Plants rich in iridoids are also useful antidotes against arthritis, diabetes, tumor, fever, wounds, hypertension and other health conditions (Dinda 2019) . Other secondary metabolites have also been identified in Psydrax including alkaloids, flavonoids and other terpenoids, and few pharmacological studies have been conducted to link the traditional uses of few species in this genus to the identified phytochemical contents.

This article reviews the ethnopharmacological uses, phytochemistry, and pharmacological properties of Psydrax genus from 1788 to September, 2021. The literature search was carried out using Google Scholar, PubMed and ScienceDirect digital repositories following the varied combination of these words: Rubiaceae, Psydrax, Canthium, ''Traditional uses'', ''folkloric medicine'', ethnopharmacology, bioactivities, ''biological activities'', ''pharmacological properties'', phytochemistry, ''phytochemical constituents'', phytochemicals. Only peer-reviewed articles written in english language were used by authors with the overall aim to inspire further studies on the genus, Psydrax, particularly its underexplored species. 

The few reported traditional uses of Psydrax species in different parts of Africa, Asia and Oceania and the forms in which they are used are summarized in Table 3 . In some of the articles, there was no distinction between stem bark and root bark; the plant part was reported just as bark. Thus, if we take the bark, root bark and stem bark to be different, then the leaf becomes the most explored plant part of the genus in ethnomedicine with about 38% of the reviewed articles reporting leaves as the plant's part used in ethnomedicine preparations, either alone or in combination with other plant parts. The trend in popularity of other plant parts is as follows: bark (approx. 21%), stem bark and root (approx. 17% each), and whole plant and aerial parts (approx. 4% each). The high popularity of the leaf of the genus in ethnomedicine is expected as the leaf is easily accessible and nondestructive of plant biodiversity (du Preez, Shingenge, and Mumbengegwi 2020). In the course of this review, it is observed that the popularity of Psydrax in traditional medicine is quite minimal when compared to other genus of the Rubiaceae family (Magassouba et al. 2007) , and this could be due to the rarity of the Psydrax species. Also observable from some of the reports on the folkoric use of these plants is that the method of preparing and the route of administration of some of the herbal medicines were omitted and only one paper reported the fidelity level for the use of the genus in traditional medicine. These obscurities could impede future scientific investigations to confirm traditional claims for the genus. Clearly seen in Table 3 is the fact that P. subcordata is the most widely used species of the genus in ethnomedicine. In Africa where P. subcordata is endemic, it is used in folkloric medicine in four specified and two unspecified African countries and this presents the species as the most popular species in African traditional medicine and Appiah and coworkers recorded a fidelity level of 50% for the use of stem bark preparation of P. subcordata in the treatment of boil in Ghana (Appiah et al. 2018) . The next most popular species in African traditional medicine is P. livida, while in Asia, specifically in India, P. dicoccos is the most explored species. In Oceania, P. odorata is the only species reported and it is used traditionally as purgative. In the course of this review, it was observed that ethnomedicinal uses of some of these plant species were reported using their synonyms. For instance, P. subcordata, P. livida, P. acutiflora, P. dicoccos and P. odorata were reported as Canthium subcordatum, Canthium huillense, Canthium henriquesianum, Canthium dicoccus and Plectronia odorata, respectively.

In four specified African countries -Cameroon, Cote d'Ivoire, Ghana and Nigeria -different parts of P. subcordata have found applications in traditional management of some ailments including the management of stomach ulcer, haemorrhoids, body pains and boils using stem bark in Ghana, (Agyare et al. 2009; Appiah et al. 2018) ; the use of an unspecified part of the plant in the management of epilepsy in Cote d'Ivoire (Daanaa et al. 2018) ; the use of root and stem bark preparation in the treatment of fever and malaria in Nigeria (Chukwujekwu et al. 2005) ; the use of the root in the treatment malaria, fever, inflammation and cardiovascular diseases in Cameroon (Awah et al. 2012) ; the use of the whole plant in the management of stomach disorders in an unspecified African country (Awantu et al. 2019) ; and the use of the bark in the management of high-blood pressure (Achenbach 1986) . It is always exciting to know that a plant species has medicinal values. However, if the activities of a plant are numerous and unrelated, it becomes a concern and requires conduction of thorough scientific investigations, including cytotoxicity assay and clinical trials, to ascertain the mechanism of action of that plant indicated for those disease conditions (Gertsch 2009 ). We therefore suggest that P. subcordata should be extensively investigated for its phytochemistry and pharmacological properties to confirm its multiple applications in folkloric medicine. The less popular species in African traditional medicine are P. horizontalis whose leaves are used in the management of diabetes in Nigeria (Feenna et al. 2020) ; in Kenya, stem bark and leaves of P. schimperiana are used for the management of breast cancer and stomachache associated with HIV infection, respectively (Ochwang'i et al. 2014 (Ochwang'i et al. , 2018 Radol et al. 2016) , while in Ethiopia, the fruit is consumed by humans as one of the edible wild fruits and the roots used for management of diarrhoea (Gemedo-Dalle et al. 2005) ; in Guinea-Bissau, barks and leaves of P. parviflora are used in treating pains (Catarino et al. 2016) , while in Guinea the root bark decoction is used for infectious diseases (Magassouba et al. 2007 ); fruits of P. livida are consumed as edible fruits in South Africa (Magwede et al. 2018) , while in Zimbabwe the leaf paste is popularly used for treating wounds (Maroyi 2012; Mukandiwa et al. 2012a, b) and ectoparasites in livestock (Nyahangare et al. 2015) .

In Asia, different parts of P. dicoccos are widely used in Indian ethnomedicine for the treatment of a variety of ailment: the leaf preparations are used for general pain relief (Chandramouli and Mallikarjuna 2020) , to ease delivery (Vaidyanathan et al. 2013) , and to treat fever, cough, asthma and inflammation ; the fruit is edible (Rasingam 2012) ; the bark powder preparation is used topically to treat rheumatic pains (Neelima et al. 2011 ); root decoction is used for the treatment of diarrhoea (Raja et al. 2011) ; the juice obtained from crushing together the leaf and bark is used to treat high blood pressure (Sen and Behera 2016) ; and in ethnoveterinary medicine, the leaves, bark and root of P. dicoccos are used as piscicides for controlling predatory fish species (Dutta et al. 2019; Kalita et al. 2017) . The leaf extract of P. umbellata, is used for the treatment of urinary tract diseases Vijayashalini et al. 2017) . In Malaysia, an unspecified part of P. livida is used in the management of diarrhoea.

In Oceania, New Caledonia to be precise, a mixture of the bark and leaves of P. odorata is used for cephalalgia, and as a purgative in combination with other plants and sea water (Sévenet and Pusset 1996) .

The few Psydrax species which have been screened for phytochemicals contain various chemical constituents such as saponins, terpenes, tannins, coumarins, glycosides and flavonoids (Akoto et al. 2019 ). Out of the over 100 species of the genus, only eight of the species including P. subcordata, P. acutiflora, P. montigena, P. livida, P. odorata, P. dicoccos, P. puberula and P. schimperiana have been explored for phytochemicals, and approximately 131 compounds were identified using different chromatographic and spectroscopic techniques. However, only the structures of fifty-five compounds (1-55) isolated from this genus and characterized using NMR and/or LC-MS techniques are given in this review. Their names are also listed in Table 4 . About half of the 55 isolated compounds of this genus are iridoids (1-27), while the remaining 50% are other terpenes (28-35), cyanogenic glycosides (36-39), alkaloids (40-42) and others we called miscellaneous compounds (43-55) because they were too small to be grouped into classes. Twenty-one of the iridoids (1-21) were isolated from different parts (stem bark, fruit and leaf) of the moderately studied species of the genus, P. subcordata, with shanziside methyl ester (21) appearing in both the stem bark and the fruit extracts of the species. The other six iridoids (22-27) were obtained from P. montigena (22) and the leaf and bark of P. odorata (23-27). Since iridoid is the most commonly encountered non-volatile chemical constituent of the genus, we adjudge it as the chemotaxonomic marker of the genus and would focus our discussion of the phytochemical importance of Psydrax on iridoid.

The rest of the phytoconstituents of the genus listed in Table 4 are volatile compounds (56-131) which were identified by GC-MS analysis. They made up more than half (about 58%) of the 131 phytochemicals of Psydrax. Forty-six of them (56-101) were identified (1) 17 Canthiumosides (2) 18 Canthiumosides (3) 19 Canthiumosides (4) 20 Canthiumosides (5) 21 Shanziside methyl ester P. subcordata SB and Fr (Achenbach et al. 1981; Achenbach 1986; Joubouhi et al. 2015 Joubouhi et al. , 2017 22 

Fr (Schwarz et al. 1996) (1) in the hexane fraction of P. puberula leaf. One major drawback of characterizing compounds with GC-MS is the ability to match accurately the compounds in a mixture with exact spectra in GC-MS spectra database. GC-MS analysis of a complex mixture is not always 100% accurate; there is a huge possibility of assigning a wrong spectra to a wrong compound. Besides, GC-MS analysis is a destructive analytical method which could cause the breakdown of compounds and ultimately lead to identification of degradation products instead of the original constituents. Thus, in this review, we discovered that some of the compounds identified by GC-MS method are not natural products (for example, (111, 116 and 117) ). For instance, (111) -a herbicide -might have accrued from the use of herbicides on the field where the plant material was harvested or it might be a product of a decomposed secondary metabolite. The expertise of the researcher in interpreting GC-MS spectra is also very important to avoid assigning wrong molecular formulae to compounds. One of the articles reviewed in this paper mistakenly gave a compound two synonymous names (furfural (102) and 2-Furancarboxaldehyde (107)) and assigned them two different molecular formulae. In summary, we will limit our phytochemistry review of the genus to isolated compounds whose structures were elucidated with other techniques (NMR, LC-MS andESI-FTICR-MS) apart from GC-MS.

Iridoids are a group of monoterpenoids recognized by their basic structure in which a pyran is fused to a cyclopentane, and are usually grouped into glycosidic, non-glycosidic, seco-and bis-iridoids (Ludwiczuk et al. 2017) . Their activities could be likened to those of adaptogens and immunomodulators, and they are considered as prodrugs that get easily converted to active pyridine monoterpene alkaloids (Ghisalberti 1998) . Chemical structures of iridoids are quite diverse and might be confusing if not well looked at because they often look alike. They play a role in ants' defence mechanism and are commonly found in plants infested with ants. Some patents have been filed for some natural iridoids in a recent review article for many biological activities (Hussain et al. 2019 ). However, many of them were in vitro investigation with most activities recorded at very high concentrations of iridoids which might be considered scientifically insignificant. For instance, in one of the patents (21) as bioactive anti-SARS agent. But all hope is not lost since iridoids are projected as pro-drugs whose activities could be greatly enhanced in vivo. It is worthy of note that some iridoids have shown good activities including cardiovascular, antihepatotoxic, hypoglycemic, hypolipidemic, anti-inflammatory, antispasmodic, antitumor, antiviral, and purgative activities (Ghisalberti 1998; Hussain et al. 2019; Tundis et al. 2008 ) at low concentrations. They are found naturally in varied forms in different plant species, and a good number has been documented for Pysdrax species. The structures of this class of compounds are captured in Fig. 1 .

In a recent study, involving the stem bark of P. subcordata, two non-gylcosidic iridoids (1 and 2) were isolated, alongside other constituents (Awantu et al. 2019) . Another set of non-glycosidic iridoids (3-8), which were novel and two known ones (9 and 10) were isolated from leaf and bark extracts of P. subcordata (Zhou et al. 2019) . The largest number of iridoids (11-21) was isolated from iso-butanol fraction Fig. 1 Iridoids and their glycosides of methanol extract of P. subcordata dried fruits, and out of the eleven iridoids, five (16-20) were novel compounds (Joubouhi et al. 2015) . Compound (22) was characterized in an extract of P. montigena using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) (Yang et al. 2016) , while (21 and 27) were obtained from the methanol extract of the stem bark of P. subcordata (Achenbach 1986; Achenbach et al. 1981) , after an initial isolation of only (27) from the same extract (Achenbach et al. 1980 ). Out of the 22 iridoids so far isolated from P. subcordata, (21) is observed to be the most common and widely distributed iridoid of the species; it was isolated as the major component of the methanol extract of dry fruits and stem bark of P. subcordata. Another species that yielded iridoids is P. odorata; its leaf and bark produced four glycosidic iridoids (23-26), in company with other non-iridoid constituents (Coulerie and Poullain 2016; Sévenet and Pusset 1996) . These data on iridoids suggest that the genus accumulates high amounts of this class of metabolites which may be of taxonomic relevance in plant systematics if further investigation is carried out.

Terpenes are a class of compounds often found abundantly in essential oils because of their high volatility, and they are usually characterized using GC-MS technique. However, in this review, eight terpenes were isolated from three species of the genus and their structures and names are given in Fig. 2 and Table 4 respectively.

A non-glycosidic terpenoid (28) was isolated and characterized with NMR technique from the stem bark of the methanol extract of P. subcordata (Awantu et al. 2019) as well as in a GC-MS analysis of the n-hexane fraction of the leaves of P. puberula (Castro et al. 2016) . The presence of (28) in two different species of the genus indicates possible similarities in the biosynthetic gene clusters of Psydrax species. In other studies, four non-glycosidic terpenoids (29-32) and three non-glycosidic terpenoids (33-35) were obtained from methanol extract of the stem bark and fruit of P. subcordata (Achenbach et al. 1981; Awantu et al. 2019; Joubouhi et al. 2015) . Cyanogenic glycosides are often considered toxic due to the ease of transformation of their aglycones to hydrogen cyanides a poisonous chemical (Yulvianti and Zidorn 2021) , and could be seen as unimportant therapeutic agents. However, a bioactivity of this class of compound was reported by Tan et al (2012) in their study of the neuroprotective effects of prunasin gallates against H 2 O 2 induced oxidative damage of NG108-15 cells. They reported in vitro neuroprotective property of highly glycosylated trigallates and tetragallate of prunasin (36), one of the compounds isolated from Psydrax, at a concentration of 100 lM of the test samples and a positive control, catechin (Tan et al. 2012) . It is obvious that this report was marred by the high concentration of test samples and the reference drug used. Also the bioavailability of these compounds are not guaranteed in vivo due to the high polarity of the glycosylated compounds and a possible loss of the sugar moiety in vivo. Apart from (36), two other cyanogenic glycosides (37 and 38) were isolated from methanol extracts of the leaf, stem and root of P. livida (Rockenbach et al. 1992 ) and the fourth cynogenic glycoside (40) was from a methanol extract of ripe fruits of P. schimperiana (Schwarz et al. 1996) . The chemical structures of these compounds are shown in Fig. 3 .

It is observed in the course of this review that alkaloid is not a common constituent of this genus and there are some conflicting claims as to whether they are present or absent in the genus. Some researchers discovered zero alkaloid when they chemically profiled the leaf, stem and root barks of P. subcordata, P. peruviana, and P. acutiflora (Denise P Ilboudo et al. 2013; Goh et al. 1997; Achenbach 1986; Achenbach et al. 1981; Daanaa et al. 2018; Akoto et al. 2019 ). On the contrary, some other research groups identified alkaloids in a different part of P. subcordata, P. horizontalis, P. schimperiana and P. dicoccos, but they reported the alkaloid content of P. schimperiana and P. dicoccos to be small (Anokwah et al. 2016; Feenna et al. 2020; Ochwang'i et al. 2016; Umaiyambigai et al. 2016) . To confirm the presence of alkaloids in Psydrax, three alkaloids: two monoterpene alkaloids (40 and 41) and a peptide alkaloid (42) were isolated from P. odorata bark and leaf (Coulerie and Poullain 2016) and their structures are given in Fig. 4 . The observed variations in alkaloid content of Psydrax species could be attributed to different factors, such as geographical differences, different harvesting seasons and analytical techniques and methods adopted by different authors and/or differences in the genetic make-up of different species of the genus. This inconsistency in the alkaloid contents of the genus calls for further extensive phytochemical studies of the genus across different geographical locations where Fig. 3 Cyanogenic glycosides the species are endemic and adoption of a standard analytical technique and method that will provide a clearer perspective on the types of alkaloids and the alkaloidal content of the genus.

Flavonoids are relatively rare in Psydrax, out of the 55 compounds isolated from the genus, only three were flavonoids: a flavone (43) isolated from the fruit of P. subcordata (Joubouhi et al. 2015 (Joubouhi et al. , 2017 , and a flavonol (44) and its glycoside (45) from P. dicoccos leaves (Gunasegaran et al. 2001) . The structures of the flavonoids are given in Fig. 5 .

The remaining ten compounds are grouped under miscellaneous because of their less popularity in Psydrax and their structures are given in Fig. 6 . They include, an aliphatic alcohol (46), an aromatic alcohol (47), a hydroxy coumarin (48), indole (49) which were obtained from the stem bark of P. subcordata (Achenbach 1986; Achenbach et al. 1981) ; chromone (50) obtained from the leaf and twig of P. acutiflora (Ilboudo et al. 2013 ); a cyclic glycoside (51) from stem bark of P. subcordata (Awantu et al. 2019 ); a glycosidic furanone (52) and aromatic ester (53) obtained from the leaf of P. livida (Nahrstedt et al. 1995) ; and two dicaffeoylquinic acids (54 and 55) isolated from the fruit of P. schimperiana (Schwarz et al. 1996) .

A few numbers of biological assays have been carried out on extracts and constituents of Psydrax species to support the acclaimed applications of these plants in the traditional management of a wide range of ailments. Unfortunately, only eight (P. subcordata, P. palma, P. acutiflora, P. montigena, P. schimperiana, P. livida, P. horizontalis and P. dicoccos) out of a hundred and thirty species of this genus, as well as P. peruviana which is not yet included in the WCSP database, have been pharmacologically tested for activities. Of the bioassays conducted for these species, majority are in vitro assays, three are in vivo studies and one is an ex vivo study. These conducted bioassays for the genus are summarized in Table 5 for record purposes, nothwithstanding the concentrations and methods used by different authors. However, only assays conducted with concentrations moderate enough to have any scientific importance are enumerated in the body of this text. It was observed by the current authors that for most in vitro assays conducted for this genus, only few of the studies performed cytotoxicity assay and determined selectivity index (SI) for their bioactive samples to verify the safety of the samples and predict their therapeutic margin. Among the species investigated for bioactivity, P. subcordata is the most explored pharmacologically, while the leaf is the most investigated plant part. P. palma was referred to as Cathium oddonnii, its synonym, in two articles that reported its bioactivity.

Some of the compounds identified in Psydrax have previously been isolated from other medicinal plants and have shown varying pharmacological properties. For instance, b-sitosterol (28) was previously isolated from the stem bark of Solanum surattense and Pterospermum acerifolium, and these plants are used in the herbal treatment of a range of diseases including diabetes (Gupta et al. 2011; Muhit et al. 2010) . In an attempt to support the traditional use of Solanum surattense in the herbal management of diabetes, Gupta et al. (2011) conducted a 21 day in vivo multiple dose (10, 15 or 20 mg/kg) antidiabetic assay of (28) as against 0.3 mg/kg of a reference drug, glibenclamide and also conducted acute toxicity assay of (28) in rats to determine the lethal dose (LD50: 120 mg/kg) of the compound (28). They reported antidiabetic activity of (28) at all doses in comparison to the positive control (0.3 mg/kg), with 20 mg/kg having the best activity among the test doses. Though the activity of (28) was adjudged good, the comparison was done at a very high concentration (20 mg/kg) of the test compound as against glibenclamide (0.3 mg/ kg). In another in vivo multiple dose (15 and 30 mg/kg for 30 days) antidiabetic study of an ethyl acetate subfraction of an ethanol extract of the bark of Pterospermum acerifolium from which (28) was isolated, the authors reported good activity at 30 mg/kg of the fraction as against 0.6 mg/kg of STD drug used in the study (Rathinavelusamy et al. 2014 ). It was not clear to us what the STD drug was in the article. Rathinavelusamy et al. 2014 after isolating (28) from the most active fraction of Pterospermum acerifolium conducted an in silico antidiabetic study to determine the inhibitory activity of (28) against the human pancreatic a-amylase (HPA). They revealed free binding energy and inhibition constant (K i ) of -8.39 kcal/mol and 0.269 lmol for (28), and -6.07 kcal/mol and 28.52 lmol for the reference drug, acarbose, and they presented (28) as a potential HPA inhibitor when compared to acarbrose (Rathinavelusamy et al. 2014 ). These reports are proof-of-concept of the potential antidiabetic property of (28) which is one of the phytoconstituents of the stem bark and leaf of a Psydrax species, P. subcordata (Awantu et al. 2019; Castro et al. 2016) . European Committee on Antimicrobial Susceptibility Testing (EUCAST), and Clininal and Laboratory Standards Institute (CLSI) provide standard methods called antimicrobial susceptibility testing (AST) for conventional antimicrobials for rational comparison among antimicrobial assay results generated by researchers (Bubonja-Š onje et al. 2020). Unfortunately, there are no such established methods for assessing the antimicrobial properties of plant materials due to the complexity of plant samples and this leads many researchers to adopting varied modified AST to achieve their desired goals (Bubonja-Š onje et al. 2020). The result of these of these incoherent test methods is the generation of incomparable, difficultto-interpret and often times misinterpreted research outcomes (Bubonja-Š onje et al. 2020; Cos et al. 2006; Eloff 2019; Gertsch 2009) . This is what was observed in the course of this review, different researchers adopted varying test methods; different concentrations of plant samples were used; test organisms and media were not similar in many cases; and endpoint parameters (MIC, IC 50 ) assessed were dissimilar (Cos et al. 2006) .

Some of the articles reviewed reported sample concentrations far above the recommended MIC value for plant extracts and pure compounds ((0.1 mg/mL (100 lg/mL) for extracts/fractions or less than 25 lM for pure compounds), and acceptable maximum in-test concentration of 1 mg/mL for plant mixtures and 0.1 mg/mL for pure plant constituents (Ríos and Recio 2005) ; many articles reported activity as minimum inhibitory concentration (MIC) values instead of (11, 13, (15) (16) (17) (18) (19) 21) In vitro Antioxidant, antibacterial, antifungal, toxicity concentration at 50% inhibition (IC 50 ), which is adjudged to be scientifically significant at a value less than 0.1 mg/mL (100 lg/mL) for extracts/fractions or less than 25 lM for pure compounds; some authors used concentration of microbial inoculum greater than the acceptable standard of 10 5 CFU/mL for bacteria and 10 3 or 10 4 CFU/mL for fungi (Cos et al. 2006) . Another crucial observation made in this review is that, some authors adopted agar diffusion method which is not a generally acceptable standard method for determining the MICs of plant extracts/fractions because of the low polarity of most plant's antimicrobial constituents which often hinders their diffusion through the polar agar medium used for the tests and ultimately leads to false negative result (Eloff 2019) . Eloff also pointed out that an MIC value less than 0.1 mg/mL is scientifically relevant for further antimicrobial studies, that anything above this benchmark should not be pursued for further investigation (Eloff 2019) . Being guided by these recommendations, we hereby enumerate only the in vitro antimicrobial assay results of extracts and pure compounds of the genus whose IC 50 /MIC value is less than 100 lg/mL for plant extract/fraction and less than 25 lM or \ 10 lg/ mL for pure compounds, as well as those that used microbial inoculum concentration of 10 5 CFU/mL for bacteria and 10 3 or 10 4 CFU/mL for fungi. To the best of our knowledge, no antimicrobial in vivo assay nor clinical trial has been reported for either the extracts nor phytoconstituents of this genus. Antimicrobial assay conducted by Awantu et al. (2019) for eight compounds (1, 2, 28, 29, 30, 34, 35 and 51) they isolated from the stem bark of P. subcordata, against three Gram positive bacteria (Staphylococcus aureus, Staphylococcus saprophiticus, Streptococcus faecalis), three Gram negative bacteria (Klebsiella pneumonia, Pseudomonas aeruginosa) and two fungi species (Candida albicans and Candida krusei) using broth dilution method showed only (1, 2 and 30) to be effective. They reported the following results for the three active compounds using gentamicin (IC 50 2.4 lg/mL) and nystatin (IC 50 4.8 lg/mL) as positive control for bacteria and fungi, respectively: (1) was active against only C. albicans (IC 50 9.7 lg/mL); (2) was active against C. albicans (IC 50 4.8 lg/mL), C. krusei (IC 50 9.7 lg/mL) and S. aureus (IC 50 9.7 lg/mL); (30) was active against C. albicans (IC 50 9.7 lg/mL), K. pneumonia (IC 50 9.7 lg/mL) and P. aeruginosa (IC 50 4.8 lg/mL) (Awantu et al. 2019) . In another study conducted by Joubouhi et al.( 2017) for the fourteen compounds (11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 31, 32 and 43) they isolated from the fruit extract of P. subcordata using micro dilution method, only (13) displayed antibacterial activity against a Gram-positive bacterium, S. aureus, with an MIC value of 8 lg/mL; they used two reference drugs -ampicillin (MIC 8 lg/mL) and ciprofloxacin (MIC 2 lg/mL). None of the compounds was active against any of the Gramnegative bacteria strains (four strains of Vibrio cholerae, and Shigella flexneri) used by the authors (Joubouhi et al. 2017) .

In a preliminary study to support the use of P. livida leaves in the traditional treatment of wound myiasis in animals, a group of researchers Mukandiwa et al. (2012b) carried out an in vitro antibacterial assay of four extracts (hexane, dichloromethane, acetone and methanol) of P. livida leaves against two Grampositive bacteria (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), which are implicated in the pathogenesis of wound myiasis, by adopting microdilution assay method. They discovered that the dichloromethane extract was the most active among the extracts. However, the dichloromethane extract was active against only S. aurus with MIC values of 78 lg/mL as against the MIC value (0.78 lg/mL) for gentamycin, the reference drug.

Antimicrobial assay conducted by Castro et al. (2016) for crude extract and three fractions (hexane, chloroform and butanol) of P. puberula leaf against S. aureus, P. aeruginosa and E. coli, using microdilution method, showed varying antimicrobial activity. The crude extract and three fractions were all active against only S. aureus with MIC values ranging from 31.25 -62 lg/mL as against the MIC value of about 3.91 lg/mL of ciprofloxacin, the positive control (Castro et al. 2016 ). An antifungal assay of P. subcordata mature fruits' essential oil against A. niger showed activity with an MIC value of 39 lg/mL in comparison to a positive control, amphotericin B (MIC value of 0.61 lg/mL) (Essien et al. 2015) ; the essesntial oil showed no significant activity against any of the bacteria species (Bacillus cereus, S. aureus, E. coli and P. aeruginosa) tested. From these enumerated antimicrobial properties, Psydrax could hold a promise in the discovery of antibacterial and antifungal agents with broad spectrum of activity. However, more research works, especially in vivo study of the active samples and cytotoxic assays, is needed to substantiate this knowledge-informed hypothesis. These few promising antimicrobial properties observed for the extracts and constituents of the genus support some of its traditional applications in the treatment of diarrhoea and wound myiasis.

It is recommended that every biological assay should be conducted by adopting a standardized procedure for the assay, using as small an amount of plant sample as possible and a standard positive control (Cos et al. 2006) . Whenever a too low or too high concentration is used, a false negative or positive result will prevail. For anti-inflammatory assays, Chukwujekwu et al. (2005) rightly observed that recording a relatively good in vitro prostaglandin synthesis inhibition for a non-polar extract as against more polar extracts does not corroborate the traditional use of the aqueous extracts in the traditional management of inflammation (Chukwujekwu et al. 2005) . The possibility of aqueous herbal extracts to elicit anti-inflammatory effect in folkloric medicine could be linked to the high phenolic content of aqueous extracts which are mainly antioxidants and could give anti-inflammatory effect by improving the immune system of the patient (Eloff 2019) . For the Psydrax genus, different in vitro and in vivo anti-inflammatory assays have been carried out for different extracts of P. subcordata and P. acutiflora, but we will only report results that used maximum in-test concentration of 1 mg/mL of plant extracts/fractions or 0.1 mg/mL of pure plant constituents in in vitro assays, and in vivo oral concentration of not more than 100 mg/kg for extracts.

Unfortunately, only the in vivo study done by Anokwah et al.( 2016) fell within our chosen concentration range. In an in vivo per oral (p.o.) antiinflammatory assay they conducted for the methanol stem bark extract of P. subcordata using carrageenaninduced footpad oedema in seven-day-old chicks, the authors reported dose-dependent percentage oedema inhibitions of 61.21, 53.00 and 49.34% at 300, 100 and 30 mg/kg body weight p.o. doses, respectively, of the extract using two positive controls, dexamethasone (0.3, 1 and 3.0 mg/kg) and diclofenac (10, 30, and 100 mg/kg) given intraperitoneally (Anokwah et al. 2016 ). Though they recorded anti-inflammatory activity for the plant extract, the concentrations used for the extract were higher than those of the positive control coupled with different routes of administration used for the test sample and the controls.

Antiparasitic assay like other anti-infection assays should follow some recommended standards previously mentioned to guarantee the authenticity of its results. Psydrax species have found applications in traditional management of malaria and fever, and in attempts to support this ethnomedicinal claim, some researchers conducted in vitro antiplasmodial assay of different extracts and constituents of the genus and they came up with varied antiplasmodial activities for the genus. However, it was observed that majority of these in vitro studies investigated either susceptible or resistant strains of Plasmodium falciparium and not both strains as deemed appropriate for a primary in vitro antiplasmodial assay (Cos et al. 2006) . For studies that determined the IC 50 of test samples (extracts), the IC 50 values they obtained were within the acceptable range of below 100 lg/mL for crude extracts, but toxicity assays were not conducted for these active extracts to confirm that the activities reported were not due to non-specific activity and potential toxicity of the extracts (Cos et al. 2006) .

In a study involving stem bark methanol extract of P. subcordata against a chloroquine resistant P. falciparum W2, there was an inhibition against the parasite with an IC 50 of 3.044 lg/mL, however, fractions and constituents (1, 2, 28, 29, 30, 34, 35 and 51) from the extract showed no activity against the parasite strain (Awantu et al. 2019) . However, the authors did not give the IC 50 value for the positive control. In another study, 80% methanol extract of P. palma, showed parasitic inhibition against a chloroquine-sensitive P. falciparum strain (positive control: chloroquine 2H 3 PO 4 -IC 50 0.08 lg/mL), Trypanosoma brucei brucei (positive control: suramin -IC 50 0.08 lg/mL), and Trypanosoma cruzi (positive control: suramin -IC 50 0.05 lg/mL), with the same IC 50 [ 64 lg/mL, using 96-well tissue culture plates method (Mesia et al. 2008) . They also conducted cytotoxicity test for the extract against the MRC-5 human cell-line and got the same IC 50 value, but they reported the extract as inactive at this IC 50 comparing its activity with the activities of extracts from other plants having IC 50 as low as 0.7 lg/mL and did not calculate the selectivity index (SI) for the extract.

In another study involving different extracts (hexane, diisopropyl ether, dichloromethane, ethyl acetate, and methanol-water) of P. acutiflora leaf/twig, tested against chloroquine susceptible and resistant strains of P. falciparum, using the parasite lactate dehydrogenase assay method, the exracts displayed variable IC 50 values against the two strains of the parasite. The diisopropyl ether extract showed highest activity against the parasite strain (IC 50 8.8 lg/mL and IC 50 9.5 lg/mL) against the susceptible and resistant strains respectively, while the ethyl acetate extract was the least active (IC 50 61.3 lg/mL) against the sensitive strain and methanol-water extract showed least activity (IC 50 64.8 lg/mL) against the resistant strain. Chloroquine used as the positive control for this study had an IC 50 of 0.20 lg/mL and IC 50 0.009 lg/ mL against the sensitive and resistant strains respectively (Ilboudo et al. 2013) . (Ilboudo et al. 2013 ) also tested the in vitro antiplasmodial activity of the most abundant constituent (50) of the diisopropyl extract and reported less activity (IC 50 18.1 lg/mL and IC 50 43.4 lg/mL) for (50) against the sensitive and resistant strains, respectively, in comparison with the diisopropyl extract. In addition to these antiplasmodial tests, (Ilboudo et al. 2013 ) also conducted cytotoxicity tests and calculated SI for the aqueous extract of P. acutiflora with IC 50 80.0 and 46.91 lg/mL against the sensitive and resistant strains of organism, respectively, and obtained a CC 50 value of 615.4 lg/mL and SI values of 7.7 and 13.1 for the sensitive and resistant strains, respectively.

In the quest to support the folkloric use of ethanol extract of P. subcordata in the management of epileptic seizures, Daanaa and co-workers used varying animal models in in vivo anticonvulsant assays of 70% ethanol extract of the leaves of P. subcordata. They explored the following animal models and reference drugs: pentylenetetrazole-induced seizure (reference drug: diazepam (0.3, 1 or 3 mg/kg, i.p.)); picrotoxin-induced seizure (reference drug: diazepam (0.3, 1 or 3 mg/kg, i.p.)); maximal electroshock (reference drug: carbamazepine (3, 10 or 30 mg/kg, p.o)); strychnine-induced seizure (reference drug: diazepam (1 mg/kg, i.p.)); 4-aminopyridine-induced seizure (reference drug: sodium valproate, (100, 300 or 600 mg/kg, p.o.)); and lithium/pilocarpine-induced status epilepticus (reference drug: diazepam (1 mg/kg, i.p.), and discovered that the extract worked by delaying the onset of seizure and reducing the duration and frequency of induced convulsions in most of the animal models, at study doses of 30, 100 and 300 mg/ kg (p.o.). However, in electroshock and strychnineinduced test models, the hydroethanol extract failed to delay the onset of tonic hind limb extensions and the onset of seizure, respectively (Daanaa et al. 2018) . Though the doses of the extract used in this study were ten times those of the reference drugs, this report by Daanaa et al. gives a pharmacological insight to the use of ethanol extract of P. subcordata leaves in the ethnomedicinal management of epileptic convulsion and presents the plant as a possible source of anticonvulsant agents if further investigated to find out if there could be any synergistic effect of using the extract in a combination therapy, since herbal medicines are often administered as a mixture of many extracts. Another way to ascertain the use of this extract in traditional medicine is by screening and isolating the active constituent(s) of the extract and carrying out extensive assays (in vitro and in vivo) on the isolated compound(s) and ultimately conduct clinical studies to substantiate their activities. This study by Daanaa et al. (2018) is the only anticonvulsant assay so far done for this genus.

In a bid to support or refute the ethnomedicinal use of P. subcordata bark in the management of diabetes, Zhou et al. (2019) carried out an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay on eight iridoids (3-10) isolated from ethanol extracts of P. subcordata leaves and bark. Only (3), one of the six novel iridoids (3-10) showed relavant enzyme inhibition with an IC 50 value of 22.2 lM in comparison with the positive control, oleanolic acid (IC 50 4.3 lM). Though this is not very fantastic, but chemical modification of the compound could lead to a better activity. To prove this assertion, when the structures of two enantiomers, subcordatanol III (5) and subcordatanol IV (6) were transformed to subcordatalactons A and B, respectively, their antihyperglycemic property dramatically improved from IC 50 value of [ 80 lM to 8.9 and 9.8 lM for A and B, respectively (Zhou et al. 2019) . We recommend in vitro cytotoxicity assay and calculation of SI for (3) as well as in vivo assays to determine its bioavailability and mechanism of action.

Since the antioxidant activity recorded for this genus was from in vitro assay, which is not a sufficient prove of a possible in vivo efficacy of the samples as antioxidants, we hereby present the in vitro radical scavenging results as an indication of the phytoconstituents of the species rather than as a bioactivity. Many a time, extracts that exhibit in vivo antioxidant property are usually high in phenolic content, But, the phytochemical analysis of the eight studied species of Psydrax gave only three flavonoids as phenolic compounds which might be considered too small to accord the genus antioxidant properties. Surprisingly, some of the extracts and isolated compounds of the genus exhibited in vitro radical scavenging properties. We decided to present in vitro radical scavenging results of extracts with IC 50 or EC 50 values less than 10 or 100 lg/mL for compounds or extracts/fractions and to exclude results with very high concentrations of no scientific relevance. In a study conducted by Awah et al. (2012) , 80% methanol root extract of P. subcordata displayed DPPH radical scavenging property with an EC 50 value of 23.9 lg/mL in comparison to ascorbic acid of EC 50 value of 4.9 lg/mL. Akoto et al. (2019) reported that the methanol extract of P. peruviana stem bark also displayed DPPH radical and hydrogen peroxide scavenging activities with IC 50 values of 12.20 and 24.26 lg/ml, respectively. Two iridoids (13 and 17) isolated from the fruit extracts of P. subcordata reportedly displayed DPPH radical scavenging activity with EC 50 values of 1.12 lg/mL and 2.03 lg/mL for (13) and (17), respectively in comparison with EC 50 of 1.74 lg/mL for vitamin C, the positive control (Joubouhi et al. 2017) . (13) and (17) are not polyphenolic compounds with inherent antioxidant properties, neither are they glycosidic, yet they exhibited radical scavenging properties. Thus, their radical scavenging properties needs further investigation -probably in vivo studies -to confirm the activity and elucidate the mechanism of action of these extracts and compounds.

Toxicity assays are very paramount in discovering new drugs to confirm the safety of any bioactive extract/fraction or compound. It is also a test of activity of a sample against malignant cells. As previously pointed out, only few researchers take the time to carry out in vitro cytotoxicity assay to test the safety of their plant samples. It is observed in the course of this review that most of the in vitro toxicity tests were done without determining the selectivity index of test samples; an important parameter needed to establish the safety of a sample to healthy cells. Daanaa et al. 2018 , in their anticonvulsant in vivo assay of the aqueous ethanol extract P. subcordata also determined the acute toxicity of the extract in animal model and reported no death in 14 days the test lasted, but observed reduced activity and sedation of the animals at doses between 300 and 3000 mg/kg body weight. In a different study, extracts and isolated constituents (62-74) of P. subcordata fruits showed no hemolysis against human red blood cells at maximum concentrations of 512 and 256 lg/mL respectively, and are adjudged to be safe to normal cells (Joubouhi et al. 2017 ). Feenna and co-researchers reported that acute toxicity and lethality assays of methanol leaf extract of P. horizontalis in rats, showed no mortality at the maximum lethal dose of 5000 mg/kg of extract (Feenna et al. 2020) . However, contrary to the forgoing non-toxic reports about the genus extracts, in a study involving 80% methanol extract of the root of P. subcordata, there was toxicity against human peripheral blood mononuclear cells (PBMC), even at extract's concentration of as low as 10 lg/mL compared to a negative control (Awah et al. 2012) . No relevant bioactive cytotoxicity of the extracts, fractions or compounds of this genus was encountered by authors in the course of this review. We therefore recommend that more toxicity assays be conducted for extracts and constituents of Psydrax species to ascertain their efficacy against abnormal cells and safety to normal cells.

We are projecting in this review that the chemotaxonomic marker for Psydrax is iridoid. This projection is evidenced in the number of iridoids (twenty-seven) isolated out of the fifty-five isolated components of the genus. The current review reveals that investigations so far carried out on Psydrax are mainly in vitro studies, with very few in vivo studies. No in silico study has been done on the isolated constituents of Psydrax, nor any clinical trial so far. The limited in vivo studies of this genus could be one of the reasons why little scientifically significant activities have been recorded for the genus considering the fact that the major constituent of the genus is iridoid, and iridoids are seen as pro-drugs which need to be biotransformed in vivo to elicit activities. Thus, in vivo assays of these plants are strongly recommended by the authors to reveal the hidden treasure of the genus. Many of the documented studies lack depth and thus require further investigation for an evidencebased application of medicinally active species within the genus. Although some documented bioactive phytochemicals reported in a few species of Psydrax correlate well with the traditional uses of the plants, many of the studies are more or less preliminary with results of some being low to be given any further scientific attention. Future research study is strongly recommended to be focused on the characterization of bioactive constituents of plant species in the genus and subsequent in vitro and in vivo studies, adopting standard bioassay and analytical methods to ensure consistent and generally acceptable results that could be pursued for potential drug leads. It is also evidenced from this review that the genus is a good source of novel compounds with varying bioactivities, which might qualify as potential leads in drug discovery. Unfortunately, only about six percent of Psydrax species have been explored for their ethnobotanical uses, phytochemicals and pharmacological properties; and this represents a lacuna that needs to be filled. There is therefore, a scientific need for further exploration of the genus in order to discover its several other ethnomedicinal applications, phytochemicals and pharmacological properties. In conclusion, authors recommend authentic in vitro, in silico, in vivo assays and even clinical trials of extracts and phytoconstituents of this genus, adopting standard assay methods. They also suggest sustainable utilization of plant resources under this genus via useinformed cultivation and domestication of medicinally important species in order to forestall the loss of species and the decline in plant biodiversity particularly in Africa where many of the species under this genus are endemic.

Authors' contributions AFA Conception and design of the work and critical revision of the manuscript. UMC Data collection, data analysis and drafting of the manuscript. FBCO Critical revision of the manuscript and final approval of the version to be published.

Funding The study has not received any kind of funding.

Data availability Not applicable.

Code availability Not applicable.

Conflict of interest There was no conflict of interest among the authors.

Ethical approval Not applicable.

Consent for publication Not applicable.

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A New Species of Psydrax (Vanguerieae, Rubiaceae) from the Gia Lai Plateau, Southern Vietnam

Types of herbal medicine used for HIV conditions in Vihiga County

GC-MS analysis of bioactive components from the ethanolic leaf extract of Canthium Dicoccum (Gaertn.) Teijsm & Binn

Ethnobotanical Studies on the wild edible plants of Irula Tribes of Pillur Valley

Evaluation of in Silico, in Vitro a-amylase inhibition potential and antidiabetic activity of pterospermum acerifolium bark

Medicinal plants and antimicrobial activity

New and known Cyanogenic glycosides from the rubiaceae

Cyanogenic glycosides from PS psydrax and oxyanthus species

A cyanogenic glycoside from canthium schimperianum

Some ethnomedicinal plants used against high blood pressure in bargarh district in Western Odisha (India)

Alkaloids from the Medicinal Plants of New Caledonia

Plant diversity, structure and regeneration potential in tropical forests of Western Ghats

Community attitudes and preferences towards woody species: implications for conservation in nawaikoke

Conservation of priority woody species on farmlands: a case study from Nawaikoke Sub-County

Genus ophiorrhiza: a review of its distribution, traditional uses, phytochemistry, biological activities and propagation

Neuroprotective activity of galloylated cyanogenic glucosides and hydrolysable tannins isolated from leaves of phyllagathis rotundifolia

The taxonomic significance of anatomical characters of the stem in the Southern African Species of Canthium s.l

The taxonomic significance of anatomical characters of the leaf in the Southern African Species of Canthium s.l

Biological and pharmacological activities of iridoids: recent developments

Phytochemical Profiles, Antibacterial and Antifungal Activity of Leaves from the Psydrax Dicoccos (Gaertn)

Studies on ethnomedicinal plants used by malayali Tribals in Kolli Hills of Eastern Ghats

Ethnomedicinal plants survey in Elanji Hill Village sathyamangalam range of reserve forest

Anthraquinones in the Rubiaceae

Bioaffinity mass spectrometry screening

Chemical diversity of plant cyanogenic glycosides: an overview of reported natural products

Protein tyrosine phosphatase 1B inhibitory iridoids from psydrax subcordata

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