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Future Journal of Pharmaceutical Sciences
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Ethnopharmacological uses, phytochemistry, pharmacology, and toxicology of Olax subscorpioidea Oliv (Olacaceae): a review

Future Journal of Pharmaceutical Sciences volume 7, Article number: 115 (2021) Cite this article

Abstract

Background

The plant Olax subscorpioidea Oliv (Olacaceae) is a shrub that is widely available in Africa. It has been used in traditional medicine to treat various diseases including asthma, pain, inflammation, gastrointestinal and central nervous system (CNS) disorders, cough, diabetes mellitus, cancer, infectious diseases, hepatic diseases, and many other diseases. Several phytochemical and pharmacological investigations were conducted on this plant. However, comprehensive information on this medicinally important plant is not available in the literature. Therefore, in this review, we aimed to provide comprehensive and critical information on all the reported ethnomedicinal uses, phytochemistry, pharmacological activities, and potential toxicity of Olax subscorpioidea to highlight its therapeutic potentials based on traditional usage and identify research gaps as a basis for further investigations to develop novel therapeutic compounds.

Main body

The available information about the plant was retrieved from the online bibliographic databases (PubMed and Google Scholar) and published PhD dissertation using the search terms Olax subscorpioidea, traditional uses, ethnomedicinal uses, phytochemistry, pharmacology, toxicology, and safety. Phytochemical studies have shown that the plant contains several bioactive compounds such as rutin, morin, quercetin, caffeic acid, santalbic acid, n-hexadecanoic acid, squalene, nonacosane, hentriacontane, and many more compounds. Also, pharmacological investigations revealed that Olax subscorpioidea has antidepressant, antiepileptic, anti-Alzheimer’s, cytotoxic, antioxidant, antihyperlipidemic, analgesic, antiinflammatory, antiarthritic, antidiabetic, anticancer, antiulcer, antimicrobial, hepatoprotective, apoptotic, antiprotease, and other CNS effects.

Conclusion

Several pharmacological studies on Olax subscorpioidea have established its ethnopharmacological uses. However, there are limited phytochemical and pharmacological studies to validate other folkloric claims of the plant. Therefore, extensive phytochemical and further pre-clinical efficacy and safety evaluations to fully establish its therapeutic potentials and elucidate its mechanisms of pharmacological actions could be necessary.

Graphical abstract

Background

Medicinal plants have been used for many years to prevent and manage diseases [1]. These medicinal plants have gained attention in traditional medicine and remain the primary source of naturally occurring drugs used in many communities worldwide [2]. Approximately 30% of the currently available drugs contain bioactive compounds obtained from medicinal plants [3]. The World Health Organization (WHO) has reported that approximately 80% of the global population relies on medicinal plants for their primary health care needs [4]. Traditional knowledge of naturally occurring products from plant sources serves as a source of nutraceuticals and plays a vital role in drug discovery and development [5]. The use of natural products, including medicinal plants as therapeutic agents, faces numerous challenges, including lack of standardization, inadequate identification, and isolation of the bioactive compounds and lack of elucidation of mechanisms of pharmacological activities and clinical trials [6].

The plant Olax subscorpioidea Oliv is a shrub or tree that belongs to the family Olacaceae. It is up to 10 m or more in height. The plant is widely distributed in Nigeria, Zaire, Senegal, and other parts of Africa [7]. The plant is a woody shrub with leafy branches, its flowers are whitish, and the fruits are round and bright yellow when ripe. The plant is commonly known in different African languages as Ifon or Ufon in Yoruba; Gwaanon kurmii or Gwaanon raafii in Hausa; Igbulu, Atu-ogili, or Osaja in Igbo; Ukpakon in Edo; Ocheja in Igala; Aziza in Nsukka; and Mtungapwezi in Swahili [8, 9]. The plant Olax subscorpioidea in its natural habitat is illustrated in Fig. 1.

Fig. 1
figure 1

Olax subscorpioidea in its natural habitat

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Several scientific studies were conducted to evaluate the bioactive compounds and therapeutic potentials of Olax subscorpioidea. However, there is no summarized information on the ethnomedicinal uses, phytochemistry, and pharmacological properties of the plant to our knowledge. Therefore, this review summarizes the ethnomedicinal uses, phytochemical components, pharmacological properties, and toxicological studies of O. subscorpioidea. We have also identified research potentials of the plant that could be explored in the future.

Botanical classification of Olax subscorpioidea

Kingdom: Plantae; Subkingdom: Tracheobionta; Superdivision: Spermatophyta; Division: Magnoliophyta; Class: Magnoliopsida; Subclass: Rosidae; Order: Santalales; Family: Olacaceae; Genus: Olax; Species: subscorpioidea [10].

Main text

Ethnopharmacological uses

The roots of Olax subscorpioidea have been used as an aphrodisiac and are topically applied to treat cutaneous and subcutaneous parasitic infections in Nigeria [11]. The roots or the stem bark of the plant are also used as a chewing stick and preparations of dento-oral herbal remedies in the Western part of Nigeria for oro-dental hygiene [12]. Additionally, the plant roots have been used to manage inflammatory and mental diseases, convulsion, pain, and cancer in Nigeria [13]. The roots are used as a decoction against diabetes mellitus and obesity [14, 15] and asthma in South-Western Nigeria and as a recipe for the management of cancer [11, 16], malaria [17], constipation, diarrhoea, and gastric ulcer [8].

The decoction of the stem, bark, and leaves of the plant has been used in the Congo Republic against rheumatism and articular pains [18], venereal diseases, and guinea worms [19]. The whole plant of Olax subscorpioidea is used alone or in combination with Eleusine indica in the northern part of Nigeria to manage anxiety, mental disorders, and infectious diseases [13, 20]. The leaves, twig, and bark are used against arthritis, rheumatism, hepatic diseases, sexually transmitted diseases (STDs), and fever and as antidotes against venomous stings and bites [21]. The leaves of Olax subscorpioidea have been used in traditional medicine in Nigeria to manage Alzheimer’s disease [22] and depression [23].

The Fruits, seeds, roots, bark, and leaves are used as a decoction in Nigeria and Cameroon to treat constipation, yellow fever, jaundice, venereal diseases, and guinea worm [19, 24]. Various parts of the plant are used in Nigeria to treat arthritis, constipation, cough, dermatosis, fever, headaches, jaundice, malaria, rheumatism, syphilis, ulcer, and many other diseases [25]. The herbal concoction of Olax subscorpioidea is used in the management of postpartum haemorrhage [26]. The plant is also used in combination with Tetrapleura tetrapteru and other plant material to manage infantile seizure [26]. The combined herbal concoction of Olax subscorpioidea, Fagara zanthoxyloides, and T. tetraptera, together with other plant material, is used to treat syphilis, stomach disorders, and gonorrhoea [26]. The summary of the reported ethnopharmacological uses of different parts of Olax subscorpioidea is presented in Table 1.

Table 1 Ethnopharmacological uses of Olax subscorpioidea and scientific confirmation of their pharmacological activity
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Phytochemistry

Preliminary phytochemical contents of Olax subscorpioidea

Preliminary phytochemical screening of the methanol leaf extract of Olax subscorpioidea and its fractions (aqueous, butanol, hexane, and ethyl-acetate) revealed the presence of saponins, tannins, steroids, cardiac glycosides, flavonoids, alkaloids, terpenoids, phenols, and carbohydrates [35, 37, 38]. Kazeem et al. reported cardiac glycosides, flavonoids, phenols, phlobatannins, terpenoids, alkaloids, steroids, and tannins in the hexane, ethyl-acetate, and acetone leaf extract of Olax subscorpioidea [15]. The plant’s ethanol leaf extract showed carbohydrates, flavonoids, phenol, steroids, tannins, and terpenoids [25]. Ishola et al. found tannins, saponins, anthraquinones, phlobatannins, steroids, cardiac glycoside, polyphenols, reducing sugars, deoxysugar, cardenolides, and flavonoids in the aqueous leaf extract of the plant [23].

The methanol root extract of the plant revealed the presence of glycosides, terpenoids, alkaloids, and steroids [8]. Additionally, Popoola et al. reported tannins, alkaloids, saponins, flavonoids, cardiac glycosides, phenols, terpenoids, and reducing sugars in the hydro-ethanolic root extract of the plant [33].

Ayandele and Adebiyi (2007) reported the presence of tannins, glycosides, and saponins in the aqueous stem bark extract of Olax subscorpioidea, while tannins, alkaloids, glycosides, flavonoids, and steroids were present in the ethanol stem bark extract of the plant [7]. The methanol stem bark extract of Olax subscorpioidea was reported to contain alkaloids, saponins, tannins, cardiac glycosides, terpenoids, and phenols [12]. Fankam et al. reported alkaloids, anthraquinones, flavonoids, phenols, tannins, and triterpenes in the methanol fruit extract of the Olax subscorpioidea [39].

Quantitative phytochemical analysis of Olax subscorpioidea

Quantitative phytochemical contents of Olax subscorpioidea are shown in Table 2.

Table 2 Quantitative phytochemical contents of Olax subscorpioidea
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Elemental contents of Olax subscorpioidea

The mineral elements present in herbal medicines are essential supplements to the bioactive compounds and are closely related to the effectiveness and potential toxic effects of traditional remedies [43]. The elemental analysis of the root and leaf extract of Olax subscorpioidea revealed the presence of calcium, copper, manganese, magnesium, sodium, zinc, potassium, aluminium, silicon, phosphorus, sulphur, chlorine, iron, cobalt, nickel, bromine, rubidium, and strontium [25, 40].

Chemical compounds isolated and identified from Olax subscorpioidea

The butanol leaves’ fraction of Olax subscorpioidea revealed rutin, morin, quercetin, and caffeic acid [31]. Oladipupo et al. identified the presence of n-hexadecanoic acid (17.6%), 7,10,13-hexadecatrienoic acid, methyl ester (0.84%), 9,17-octadecadienal, (Z)- (2.87%), 9,12-octadecadienoic acid (Z,Z)- (18.0%), octadecanoic acid (4.05%), squalene (4.12%), nonacosane (5.54%), and hentriacontane (1.22%) in the n-hexane leaf extract of the plant [44]. Additionally, santalbic acid was isolated from the methanol seed fraction of Olax subscorpioidea [45]. The phytochemical constituents identified and isolated from Olax subscorpioidea are illustrated in Table 3. The chemical structures of the major isolated compounds from Olax subscorpioidea are presented in Fig. 2.

Table 3 Chemical compounds isolated and identified from Olax subscorpioidea and their reported pharmacological activities
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Fig. 2
figure 2

Chemical structures of isolated compounds from Olaxsubscorpioidea

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Pharmacological activities of Olax subscorpioidea

The extracts and fractions of various parts of Olax subscorpioidea were screened for various pharmacological activities, namely antidepressant, anticonvulsant, sedative, anxiolytic, anti-Alzheimer’s, cytotoxicity, antioxidant, hypolipidemic, analgesic, antiinflammatory, antiarthritic, hypoglycaemic, antiulcer, anticancer, antimicrobial, anthelmintic, hepatoprotective, apoptotic, and antiprotease activities. The summary of the reported pharmacological activities of different extracts and fractions obtained from various parts of Olax subscorpioidea are presented in Table 4.

Table 4 Reported pharmacological activities of Olax subscorpioidea
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Antidepressant activity

The ethanol leaf extract of Olax subscorpioidea significantly reduced the immobility time in forced swimming test (FST) and tail suspension test (TST) and reduced the number of crossing activity in the open field test (OFT) [13]. The results also demonstrated a significant reduction in diarrhoea in the reserpine model of depression [13]. Adeoluwa et al. reported the possible involvement of adrenergic, dopaminergic, and serotonergic systems in the antidepressant activity of Olax subscorpioidea [31]. Several antidepressant drugs such as tricyclic antidepressants and monoamine oxidase inhibitors reduce immobility time [46]. Also, antidepressant drugs including imipramine blocked reserpine-induced diarrhoea [47]. Studies have shown a correlation between adrenergic dysfunction and pathophysiology of depression [48, 49]. The (α1 and α2)-adrenergic system serves as a target for the antidepressant drugs [50]. Previous research by Yamada et al. reported the antidepressant action of drugs via dopaminergic system [51]. The serotonin reuptake inhibitors increase the synaptic concentration of serotonin [52] Therefore, the results justified the traditional use of the Olax subscorpioidea in the management of mental illness, including depression.

Anti-Alzheimer’s activity

The aqueous leaf extract of Olax subscorpioidea demonstrated promising inhibitory effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) [22]. Therefore, the plant can potentially manage Alzheimer’s disease due to its inhibitory action on the key enzymes (AChE and BChE) associated with the disease [22].

Anticonvulsant activity

The ethanol and methanol leaf extracts of Olax subscorpioidea significantly delayed the onset of seizures and death latency, which provided the scientific basis for using the plant in traditional medicine for the management of convulsion which could be due to the enhancement of gamma-aminobutyric acid (GABA) [29, 30].

Sedative effects

The ethanol leaf extract of Olax subscorpioidea produced a significant and dose-dependent reduction in rearing and grooming frequency, suggestive of its sedative and stress attenuating effects due to its interaction with α2-adrenergic pathway [29]. The extract at 25 mg/kg also significantly reduced the locomotor activity in a similar manner to diazepam (2 mg/kg), indicative of its central nervous system (CNS) depressant effect [29]. Furthermore, the extract produced a significant and dose-dependent reduction in the number of head dip and prolonged the pentobarbitone-induced sleeping time [29]. The study supports the folkloric claim of the plant in the management of mental illness.

Anxiolytic effect

The leaves of Olax subscorpioidea did not significantly alter the frequency of open arm entries and the percentage of open arm duration, which indicated its lack of anxiolytic effect [29]. Therefore, based on the reported traditional use of Olax subscorpioidea in the management of anxiety, other parts of the plant are recommended to be thoroughly screened for the folkloric claimed anxiolytic activity with other extracts or fractions that may contain potential anxiolytic compounds.

Antihyperlipidemic activity

The ethanol root extract of Olax subscorpioidea at 200 and 400 mg/kg significantly reduced the total cholesterol, triglycerides, and low-density lipoprotein and increased the high-density lipoprotein [14]. The result validated the lipid-lowering effect of the plant in the management of obesity in traditional medicine

Cytotoxic activity

Cantrell et al. reported the cytotoxicity effect of the methanol seed extract of Olax subscorpioidea. In the same study, santalbic acid isolated from the plant also showed remarkable cytotoxicity [45].

Antioxidant activity

The aqueous leaf extract of Olax subscorpioidea exerted 2,2-azino-bis-3-ethylbenthiazoline-6-sulphonic acid (ABTS) scavenging activity, iron chelating and reducing effects, and iron-induced lipid peroxidation due to the presence of high TPC [22]. The hydroethanolic leaf extract of Olax subscorpioidea produced a dose-dependent reduction in the levels of thiobarbituric acid reactive substances (TBARS) and increased the antioxidant power as well as 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity [21]. In another study conducted by Konan et al., the plant’s ethanol and aqueous leaf extracts produced a significant radical scavenging activity, inhibitory effect on lipid peroxidation, and ferric ion chelating activity and reducing power [41].

The ethanol root extract of Olax subscorpioidea demonstrated a significant antioxidant effect against DPPH radicals [14, 28]. The hydro-alcoholic root extract of the plant also showed a significant effect against nitric oxide (NO) radicals in a similar manner to ascorbic acid but higher than gallic acid [28]. In the same study, the extract significantly increased the levels of glutathione (GSH) and superoxide dismutase (SOD) and reduced the levels of malondialdehydes (MDA) [28]. The findings suggested that the plant can enhance the antioxidant activities of GSH and SOD and inhibit lipid peroxidation [28]. The methanol leaves and spice extract of Olax subscorpioidea elicited DPPH radical and hydroxyl radical scavenging activities and remarkable ferric reducing antioxidant power (FRAP) and total antioxidant capacity [32, 42].

Analgesic activity

The leaf extracts of Olax subscorpioidea showed a significant and dose-dependent reduction in the number of abdominal writhes and reduced pain responses [18, 37] suggestive of its central and peripheral analgesic activity [53]. Similarly, the extracts produced a significant increase in the pain latency in the hot plate test, which affirms its central analgesic property [10, 18]. It was concluded that the analgesic action of the extract involves its interaction with the opioidergic system [10, 18].

In another study by Odoma et al., the hexane, butanol, and aqueous leaf fractions of Olax subscorpioidea produced a significant and dose-dependent reduction in the number of abdominal writhes and pain perception in formalin-induced paw licking [37]. The aqueous and butanol fractions also demonstrated a significant and dose- and time-dependent increase in pain latency in hot plate test [37]. The mechanism of analgesic action of the butanol fraction was suggested to be due to its interaction with serotonergic and nitric oxide l-arginine pathways [9].

The aqueous leaf extract of Olax subscorpioidea showed a significant and non-dose-dependent reduction in the mean number of abdominal constrictions [23]. The extract at 50 mg/kg produced the highest activity (68.28%) in a similar manner to the standard drug, ibuprofen (67.74%). Also, at the dose of 200 mg/kg, the extract significantly reduced paw licking duration and biting in formalin-induced pain [23]. The extract at the doses of 50 and 400 mg/kg significantly and time-dependently increased the pain latency [23]. The authors concluded that the extract’s probable mechanisms of analgesic activity involve its interaction with serotonergic, KATP channels, and dopaminergic systems [23].

In another study conducted by Popoola et al. in 2016, the hydro-ethanolic root extract of Olax subscorpioidea significantly and dose-dependently reduced the number of abdominal constrictions [33]. Similarly, the extract at 200 and 400 mg/kg significantly reduced the paw licking in formalin-induced pain [33]. These findings validated the use of the plant in traditional medicine for the management of pain.

Antiinflammatory activity

The methanol leaf extract of Olax subscorpioidea and fractions (hexane, aqueous, and butanol) produced remarkable antiinflammatory effects [23, 37]. Moreover, the aqueous leaf extract of Olax subscorpioidea produced a significant and time-dependent reduction in the complete Freund’s adjuvant (CFA)-induced chronic inflammation. The extract showed its maximum inhibitory effect (85.30%) at 400 mg/kg similar to the standard antiinflammatory agent, celecoxib [23]. In a study conducted by Popoola et al. in 2016, the hydro-ethanolic root extract of Olax subscorpioidea showed a significant and dose-dependent antiinflammatory effect [33].

Research by Odoma et al. has shown that the aqueous and butanol leaf fractions of Olax subscorpioidea significantly reduced the concentrations of the pro-inflammatory cytokines, including interleukin-1α (IL-1α), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF); with no effect on tumour necrosis factor-α (TNF-α) and IL-2 [54]. In contrast, the fractions stimulate the synthesis of antiinflammatory cytokines such as IL-5, IL-6, and interferon-γ (IFN-γ) [54]. These findings validated the use of the plant in traditional medicine for the management of inflammatory disorders.

Antiarthritic activity

The aqueous and ethanol root extracts of Olax subscorpioidea significantly reduced the paw size, C-reactive protein, rheumatoid factor, erythrocyte sedimentation rate (ESR), and cytokines in a dose- and time-dependent manner compared to the arthritis-induced group [27]. The extracts also significantly reduced the synovial hyperplasia in a similar manner to indomethacin used as a standard agent [27]. The study validated the folkloric use of the plant in the management of rheumatoid arthritis.

Antihyperglycaemic activity

The hexane, ethyl-acetate, and acetone leaf extract of Olax subscorpioidea produced remarkable inhibitory effects on α-amylase and α-glucosidase, the critical enzymes associated with diabetes mellitus [15]. The hexane and ethyl-acetate extracts demonstrated higher inhibitory effects on α-amylase than the standard hypoglycaemic agent, acarbose [27]. The hexane extract produced higher α-glucosidase inhibitory activity than the acarbose [27]. In the same study, the hexane extract significantly reduced the postprandial blood glucose level [27].

Based on the study conducted by Ayoola et al., the methanol leaf extract of Olax subscorpioidea showed a non-significant hypoglycaemic effect in normoglycaemic rats, suggestive of its lack of hypoglycaemic effect on non-diabetic subjects [32]. The extract demonstrated a significant and dose- and time-dependent antihyperglycaemic effect higher than that of the glibenclamide [32]. Also, the aqueous fraction of the extract (400 mg/kg) demonstrated a similar antihyperglycaemic effect (36.87%) to the glibenclamide (38.97%) [32]. These findings validated the use of the plant in traditional medicine for the management of diabetes mellitus.

Antiulcer activity

The methanol root extract of Olax subscorpioidea produced dose-dependent ulcer protection, which was significant at the dose of 600 mg/kg in a similar manner to the standard drug sucralfate [8]. Therefore, the roots of the plant could have antiulcer activity as claimed in traditional medicine.

Anticancer activity

The hydro-alcoholic root extract of Olax subscorpioidea significantly and dose-dependently inhibited the growth of Allium cepa root [28]. The extract also produced a significant mito-depressive effect on the onion bulb similar to the standard anticancer drug, cyclophosphamide [28]. Additionally, the extract significantly increased the deoxyribonucleic acid (DNA)-damaging effect [28]. The result provided the potential chemopreventive and chemotherapeutic effect of the plant in traditional medicine against cancers [28].

Antimicrobial activity

The aqueous stem extract of Olax subscorpioidea demonstrated narrow-spectrum antimicrobial activity against Pseudomonas aeruginosa and Proteus vulgaris. In contrast, the plant’s ethanol stem extract showed broad-spectrum antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella spp., Aspergillus niger, and Aspergillus tamari [7].

The methanol seeds and stem bark extracts of Olax subscorpioidea produced remarkable antimicrobial activity against Aspergillus fumigatus and Staphylococcus aureus [34]. In other studies, the fruit extract of Olax subscorpioidea demonstrated remarkable antimicrobial activity against Candida albican, Cryptococcus neoformans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Providencia stuartuii [24, 39]. Furthermore, the extract at 2000 mg/kg significantly decreased the fungal load in the blood and kidneys of the yeast-infected rats [24].

The ethanol leaf extract of Olax subscorpioidea produced significant and concentration-dependent inhibitory effect against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Aspergillus niger, and Penicillium sp. [25]. The extract at 500 mg/ml showed better antifungal activity against Aspergillus niger and Penicillium sp. than the standard antifungal drug, fluconazole [25]. A previous research by Idowu et al. has shown that the methanol root extract of Olax subscorpioidea produced a concentration-dependent inhibitory effect against Bacillus anthracis, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, and multi-drug resistant Escherichia coli implicated in urinary tract infection [55]. The roots of Olax subscorpioidea produced inhibitory effects against Shigella spp., Escherichia coli, and Proteus spp. [56].

The studies conducted on Olax subscorpioidea validated its use for the treatment of infectious diseases in traditional medicine. However, most of the studies concentrated on in vitro investigations. Therefore, more antimicrobial evaluations using in vivo assays should be conducted with specific microbial strains to validate these results. Furthermore, investigations are required to determine the plant’s effects against multi-drug resistant microorganisms and evaluate its mechanisms of antimicrobial actions to develop novel antimicrobial agents.

Antihelmintic activity

Kone et al. reported the antihelmintic activity of the ethanol root extract of Olax subscorpioidea against Echinostoma caproni, Schistosoma mansoni, Trichuris muris, and Heligmosomoides bakeri [36]. The extract non-significantly reduced the total and female worm burden against Schistosoma mansoni [36]. Therefore, the result validated the use of the plant as a herbal remedy in the treatment of parasitic diseases such as helminthiasis.

Hepatoprotective activity

The hydro-ethanolic leaf extract of Olax subscorpioidea significantly reduced the levels of serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) compared with the carbon tetrachloride (CCl4) intoxicated group [21]. The extract at the doses of 25 and 100 mg/kg reduced the level of gamma-glutamyl transferase (GGT) and total bilirubin [21]. Also, the extract dose-dependently increased the level of (α1, α2, β, and γ)-globulin [21]. The extract at the dose of 100 mg/kg revealed near-normal hepatic cells with a mild degree of inflammation and lesser fatty infiltration without necrosis compared to the CCl4-intoxicated animals [21]. The result validated the folkloric use of the plant for the management of liver diseases in traditional medicine.

Apoptosis-induced activity

The methanol leaf extract of Olax subscorpioidea induced mitochondrial membrane permeability transition pore opening [38]. The extract also significantly increased mitochondrial adenosine triphosphate (ATP) hydrolysis and produced significant mitochondrial membrane lipid peroxidation [38]. Therefore, the plant may contain bioactive components that could help manage diseases that require an enhanced rate of apoptosis, such as cancer [57].

Antiprotease and membrane stabilizing activities

The saline and alkaline extracts of Olax subscorpioidea demonstrated remarkable antitryptic and dose-dependent membrane stabilizing activities [26]. These findings justify the use of the plant in the treatment of inflammatory-related diseases.

Phytotoxic activity

Olubode et al. reported the inhibitory effect of the aqueous extracts of Olax subscorpioidea parts (leaf, seed, bark, stem, and root) on maize germination. The extract remarkably reduced seed germination, and significantly increased the number of leaves, plant height, and root and shoot dry weight. The finding revealed that the plant possesses alloallelopathic activity on seed maize that could be useful as bioherbicide [58].

Toxicological studies on Olax subscorpioidea

There has been an upsurge in the use of herbal medicines to treat many diseases. However, some naturally occurring chemical substances have potential toxicity effects, and their safety is an essential point of health concern [59]. In the process of drug development, there are various pre-clinical toxicity studies needed, including acute toxicity study, repeated dose toxicity study, genetic toxicity study, reproductive toxicity study, carcinogenicity study, and toxicokinetic evaluations [60]. Safety information on traditional herbal medicines consumed is vital as part of a response to public health concerns [4]. Yuet Ping et al. suggested the need to document experimental information on medicinal plants’ safety profile and their extracts used in drug development [61]. Therefore, reports and data on medicinal plants’ potentially toxic effects are vital in their development for therapeutic use [4].

Acute toxicity on Olax subscorpioidea

The intraperitoneal (i.p) median lethal dose (LD50) of the methanol and ethanol leaf extract of Olax subscorpioidea was estimated to be 3800 mg/kg [30] and 300 mg/kg [29] respectively, while the oral LD50 of the methanol leaf extract of Olax subscorpioidea was estimated to be higher than 5000 mg/kg [35]. The acute toxicity study of the methanol root extract of Olax subscorpioidea showed an LD50 of 2154 mg/kg [8].

The hydro-ethanolic leaf extract of. Olax subscorpioidea (500, 1000, 2000, and 4000 mg/kg) caused some behavioural changes and mortality in mice [21]. The extract also produced signs of acute toxicity, including agitation, aggression, body twisting, convulsion, and diarrhoea at 2000 and 4000 mg/kg. Also, the LD50 of the extract was estimated to be 1000 mg/kg in mice [21].

The acute oral administration of the aqueous leaf extract of Olax subscorpioidea (500, 2500, and 5000 mg/kg) did not cause mortality in mice at all doses [23]. However, the extract produced abdominal constrictions, sedation, diarrhoea, and decreased motor activity [23]. The oral LD50 of Hepacare (a herbal formulation consist of Olax subscorpioidea and Capsicum frutescens) was 3807.89 mg/kg [62].

Sub-acute toxicity on Olax subscorpioidea

The sub-acute oral administration of the ethanol leaf extract of Olax subscorpioidea (250, 500, 750, and 1000 mg/kg) caused a significant decrease in the serum levels of alanine aminotransferase (ALT) and total bilirubin at 250 and 500 mg/kg, respectively [63]. The extract caused a significant increase in ALP at 500, 750, and 1000 mg/kg and increased plasma albumin levels at 1000 mg/kg [63]. There was also a significant reduction in mean corpuscular haemoglobin (MCH), lymphocyte (LYMP), white blood cell (WBC), and haemoglobin (HB). However, the neutrophils (NEU) significantly increased at 1000 mg/kg. The extract did not significantly change the levels of red blood cells (RBC), packed cell volume (PCV), mean corpuscular volume (MCV), platelet (PLT), and mean corpuscular haemoglobin concentration (MCHC). Similarly, there were no histopathological changes in the livers and kidney at all doses [63].

Abiodon et al. also reported the sub-acute toxicity effects of Hepacare (a herbal formulation consisting of Olax subscorpioidea and Capsicum frutescens) [62]. The herbal product has no effect on the body weight, relative heart, liver, kidney, spleen, and lung weights [62]. The ALP remarkably elevated at the dose of 750 mg/kg. Besides, ALT, AST, ALP, bilirubin, and total protein significantly increased at the dose 2500 mg/kg. The effects of the herbal combination on haematological parameters showed a significant elevation in monocytes counts with no effects on PCV, WBC, neutrophils, and lymphocytes [62]. The herbal product also revealed an evidence of hepatic and renal damage after 28-day period pf administration. In contrast, Adebayo et al. reported a lack of hepatotoxicity and renal toxicity of Olax subscorpioidea following the 28-day treatment [63].

Genotoxicity study on Olax subscorpioidea

The n-hexane leaf extract of O. Olax subscorpioidea (50 mg/kg) significantly reduced the DNA fragmentation in both the liver and testis compared with the control group [44]. Additionally, the extract produced a significant reduction in the levels of HB, PCV, RBC, NEU, and monocytes (MID), suggestive of deleterious effects of the extract on blood production, which may result in anaemia. However, the extract significantly increased WBC, LYMP, MCV, MCH, and MCHC compared with the control group [44].

Conclusion

Studies on Olax subscorpioidea have established some of the plant’s ethnopharmacological uses and provided its therapeutic potentials against many diseases. However, there are limited studies on its pharmacological activities that could further validate many reported folkloric claims. Therefore, detailed pharmacological investigations are required in the future on different parts of the plant to validate their traditional uses. Few studies were conducted to identify and isolate the phytochemical compounds present in different parts of the plant. Besides, detailed pharmacological investigations to explore their biological effects were lacking. Therefore, there is a need for more research in the future on bioassay-guided fractionation, isolation, and characterization of the extracts and fractions of Olax subscorpioidea to determine the active compounds responsible for the pharmacological activities. Moreover, the available isolated compounds could be screened for detailed pharmacological activities in animal models to explore their mechanisms of actions and molecular targets that would enable the discovery of lead compounds to develop novel therapeutic agents. Human clinical trials should also be performed to establish the clinical safety and efficacy of Olax subscorpioidea for use in the treatment of various diseases. However, the plant has the potential of causing toxicity through interfering with haematological parameters. Therefore, it should be used cautiously in patients at high risk of blood-related disorders such as anaemia. Also, further toxicity evaluations (chronic, mutagenicity, carcinogecity, teratogenicity, reproductive toxicity) of all parts of this plant are needed. Besides, more researches are required to standardize the appropriate dosage of Olax subscorpioidea for the claimed therapeutic use in traditional medicine.

Availability of data and materials

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Abbreviations

ABTS:

2,2-Azino-bis-3-ethylbenthiazoline-6-sulphonic acid

AChE:

Acetylcholinesterase

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

ATP:

Adenosine triphosphate

BChE:

Butyrylcholinesterase

CCl4 :

Carbon tetrachloride

CFA:

Complete Freund’s adjuvant

CNS:

Central nervous system

DNA:

Deoxyribonucleic acid

DPPH:

1,1-Diphenyl-2-picryl-hydrazyl

EGF:

Epidermal growth factor

ESR:

Erythrocyte sedimentation rate

FRAP:

Ferric reducing antioxidant power

FST:

Forced swimming test

GABA:

Gamma-amino-butyric acid

GAE/g:

Gallic acid equivalent per gram of the extract

GGT:

Gamma-glutamyl transferase

GSH:

Glutathione

HB:

Haemoglobin

IFN-γ:

Interferon-γ

IL:

Interleukin

KATP :

Potassium adenosine triphosphate

LD50 :

Median lethal dose

LYMP:

Lymphocytes

MDA:

Malondialdehydes

MCH:

Mean corpuscular haemoglobin

MCHC:

Mean corpuscular haemoglobin concentration

MCV:

Mean corpuscular volume

MID:

Monocytes

MRSA:

Methicillin-resistant S. aureus

NEU:

Neutrophils

NO:

Nitric oxide

OFT:

Open field test

PCV:

Packed cell volume

PLT:

Platelet

QAE/g:

Quercetin equivalent per gram of dried extract

RBC:

Red blood cell

SGOT:

Serum glutamate oxaloacetate transaminase

SGPT:

Serum glutamate pyruvate transaminase

SOD:

Superoxide dismutase

STDs:

Sexually transmitted diseases

TBARS:

Thiobarbituric acid reactive substances

TNF:

Tumour necrosis factor:

TPC:

Total polyphenol content

TST:

Tail suspension test

VEGF:

Vascular endothelial growth factor

WBC:

White blood cells

WHO:

World Health Organization

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Acknowledgements

The authors are thankful to all members of Young Pharmacists Scholars (YPS), a mentorship forum for their continuous support and guidance.

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Author information

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Kaduna, Nigeria

    Mubarak Hussaini Ahmad, Sagir Mustapha & Musa Aminu

  2. School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tas, 7005, Australia

    Abubakar Ibrahim Jatau

  3. College of Pharmacy, Riyadh Elm University, Riyadh 11681, Saudi Arabia

    Omar Yahya Alshargi

  4. Department of Pharmacology and Therapeutics, Bayero University, Kano, Nigeria

    Sa’adatu Muhammad Julde, Auwal Adam Bala & Abubakar Sadiq Wada

  5. School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Pulau Pinang, Malaysia

    Mustapha Mohammed

  6. Department of Clinical Pharmacy and Pharmacy Practice, Ahmadu Bello University, Zaria, Kaduna, Nigeria

    Mustapha Mohammed

  7. Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Kaduna, Nigeria

    Surajuddeen Muhammad

  8. Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia

    Sagir Mustapha

  9. Department of Pharmacology, College of Medicine and Health Sciences, Federal University, Dutse, Jigawa, Nigeria

    Auwal Adam Bala

  10. Department of Pharmacology, Bauchi State University, Gadau, Bauch State, Nigeria

    Abba Musab Usman

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  1. Mubarak Hussaini Ahmad
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Contributions

MHA: conceptualization, designing of the work, writing of the original draft, and editing. AIJ: critically reviewed the whole manuscript. OYA: writing and review. JMS: writing and review. MM: writing and review. SM: writing and review. SM: writing and review. AAB: writing and review. ASW: writing and review. MA: writing. AMU: writing. All the authors have read and approved the manuscript.

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Ahmad, M.H., Jatau, A.I., Alshargi, O.Y. et al. Ethnopharmacological uses, phytochemistry, pharmacology, and toxicology of Olax subscorpioidea Oliv (Olacaceae): a review. Futur J Pharm Sci 7, 115 (2021). https://doi.org/10.1186/s43094-021-00264-w

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