Aridanin and oleanane-3- O-ß-D-glucoside-2'-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines. MATERIALS AND METHODS: Eight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed. RESULTS: Out of the eight (1-8) isolates from T. tetraptera only oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin showed potent cell growth arrest with an estimated CC50 of 15, 23, 16 and 17, 26, 16 µg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin at 10 µg/mL were noticed. Oleanane-3-O-ß-D-glucoside-2'-acetamide and aridanin at 2.5 and 10 µg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145 cells and increased the adherence of DU145 cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin ß-1 (10 µg/mL) and integrin ß-4 (2.5 µg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8-18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated. CONCLUSIONS: This study outlines for the first time, the anticancer ability of compounds oleanane-3-O-ß-D-glucoside-2'-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action.

Optimized pressurized hot water extraction, HPLC/LC-MS characterization, and bioactivity of Tetrapleura tetraptera L. dry fruit polyphenols.

Despite the global preference for green extraction methods in the recovery of plant bioactives, Tetrapleura tetraptera fruit polyphenols (TTP) are yet to receive considerable attention. For the first time, pressurized hot water extraction (PHWE) of TTP was optimized for total phenol content (TPC) and antioxidant activity (AA) using the Box Behnken design of response surface methodology. Predictor variables were time, temperature, and liquid-to-solid ratio. An optimum solution with a desirability of 0.805 was selected and parameters were 43 min, 220°C, and 60 ml g-1 liquid-to-solid ratio, yielding TPC of 8.92 mg gallic acid equivalent per gram of sample on dry weight basis (GAE g-1  dw-1 ) and AA of 70.35%. Purified, optimized TTP were characterized and quantified using HPLC/LC-MS. PHWE mainly extracted rutin (379.04 µg g-1 ), cyanidin-3-O-glucoside (chloride) (299.55 µg g-1 ), naringenin 7-O-glucoside (240.11 µg g-1 ), p-coumaric acid (177.28 µg g-1 ), isorientin (150.43 µg g-1 ), and gallic acid (118.06 µg g-1 ) whereas cyanidin-3-O-glucoside (chloride) (83.27 µg g-1 ), protocatechuic acid (61.37 µg g-1 ), rutin (28.03 µg g-1 ), and gallic acid (22.62 µg g-1 ) were mainly extracted by hot water extraction, which was a control. PHWE-obtained TTP showed higher cellular antioxidant activity, cytotoxicity in human liver cancer cell lines (HepG2), and antimicrobial property against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis than control. The potential mechanisms underlying the biological activities of some of the major polyphenols extracted were briefly discussed. Considering the wide use of the T. tetraptera (TT) fruit in Africa in foods and medicine, the use of more efficient green extraction methods such as PHWE is recommended. PRACTICAL APPLICATION: This study serves as a baseline for optimizing pressurized hot water extraction, purification, identification, and quantification of Tetrapleura tetraptera polyphenols (TTP) and their biological activities, being the first of its kind. The varied biological effects shown can be exploited further for applications of TTP as nutraceutical agents and preservatives in foods in different forms. Also, the high amounts of gallic acid and other phenolic acids and flavonoids confirmed in this study make TTP good candidates for the development of metal-phenol network nanoparticles to enhance adequate solubility and distribution in food systems in light of the above proposed applications.

Phytochemical composition, bioactive properties, and toxicological profile of Tetrapleura tetraptera.

The use of medicinal plants has gained renewed wide popularity in Africa, Asia, and most parts of the world because of the decreasing efficacy of synthetic drugs. Thus, natural products serve as a potent source of alternative remedy. Tetrapleura tetraptera is a medicinal plant with cultural and traditional significance in West Africa. In addition to the plant being commonly used as a spice in the preparation of traditional spicy food for postpartum care it is also widely used to constitute herbal concoctions and decoctions for treatment of diseases. This review aimed to provide an up-to-date information on the ethnomedicinal uses, pharmacological activities and phytoconstituents of T. tetraptera. Preclinical studies regarding the plant's toxicity profile were also reviewed. For this updated review, literature search was done on PubMed, Science Direct, Wiley, and Google Scholar databases using the relevant keywords. The review used a total of 106 papers that met the inclusion criteria from January 1989 - February 2022 and summarised the bioactivities that have been reported for the rich phytoconstituents of T. tetraptera studied using various chemical methods. Considering the huge report, the review focused on the antimicrobial and antiinflammatory activities of the plant extracts and isolated compounds. Aridan, aridanin and several bioactive compounds of T. tetraptera have shown pharmacological activities though their mechanisms of action are yet to be fully understood. This study also highlighted the influence of plant parts and extraction solvents on its biological activities. It also presented data on the toxicological profile of the plant extracts using different models. From cultural uses to modern pharmacological research the bioactive compounds of T. tetraptera have proved effective in infectious disease management. We hope that this paper provided a robust summary of the biological activities and toxicological profile of T. tetraptera, thus calling for more research into the pharmacological and pharmacokinetic activities of natural products to help combat the growing threat of drug resistance and provide guidelines for their ethnomedicinal uses.

Chemical composition, antibacterial efficacy, and antioxidant capacity of essential oil and oleoresin from Monodora myristica and Tetrapleura tetraptera in Southeast Nigeria.

Specific to the West African sub-region, previous studies involving fruit, stem, and bark of Tetrapleura tetraptera as well as seeds of Monodora myristica have largely focused on phytochemical properties of aqueous and methanolic and ethanolic extracts. To supplement existing information, the chemical composition, antibacterial efficacy (tested against Escherichia coli and Staphylococcus aureus), and antioxidant capacity (1,1-diphenyl-2-picrylhydrazyl (DPPH∙) radical scavenging, ferric reducing power, and total antioxidant capacity) of essential oil and oleoresin extracted from T. tetraptera fruit and M. myristica seeds cultivated in Southeast Nigeria, were studied. Essential oil and oleoresin were respectively extracted by steam distillation and aqueous maceration. By way of gas chromatograph mass spectrometry (GC-MS) analysis, the chemical compounds from essential oil and oleoresin from M. myristica and T. Tetraptera samples totaled 6 and 5, as well as 27 and 16, respectively. Besides the oleoresin of M. myristica and the essential oil of T. tetraptera showing some resistance against S. aureus, the oleoresins seemed highly susceptible to E. coli-all of which demonstrated concentration-dependence to the antibacterial inhibition zone. Scavenging DPPH radical, reduction power activity, and total antioxidant capacity increased with essential oil and oleoresin extracts' concentrations, which positions M. myristica and T. tetraptera spices as very promising for food preservation, especially against autoxidation and microbial spoilage.

Cytotoxicity, acute and sub-chronic toxicities of the fruit extract of Tetrapleura tetraptera (Schumm. & Thonn.) Taub. (Fabaceae).

BACKGROUND: Tetrapleura tetraptera is a medicinal spice traditionally used to treat cancer, diabetes, and several other ailments. This study analyzed the cytotoxicity of the dichloromethane methanol extract of T. tetraptera fruits (TTF) and its constituents. The toxicity profile of the TTF extract was also evaluated in rats. METHODS: The Cytotoxicity of this extract was evaluated using the resazurin reduction assay (RRA). Acute and sub-chronic toxicity studies were performed according to the protocol described by the Organisation for Economic Cooperation, and Development (OECD). Hematological, serum, and urine biochemical parameters, as well as histological sections of the liver and kidney, were also evaluated based on standard methods. RESULTS: The TTF extract, compound 5, and the reference drug doxorubicin were active in all 9 tested cancer cell lines. The recorded IC50 ranged from 18.32 µM (against B16-F1 murine melanoma cells) to 36.18 µM (against SKMel-505 BRAF wildtype melanoma cells) for TTF, from 10.02 µM (towards MaMel-80a BRAF-V600E homozygous mutant melanoma cells) to 31.73 µM (against SKMel-28 BRAF-V600E homozygous mutant melanoma cells) for compound 5, and from 0.22 µM (against B16-F1 cells) to 9.39 µM (against SKMel-505 cells) for doxorubicin. The study of acute toxicity test showed that the lethal dose (LD50) of this extract was greater than 5000 mg/kg body weight. In the sub-chronic toxicity studies, variations were observed in some biochemical parameters, especially at higher doses. CONCLUSION: TTF and its most active compound (5) are found to be potential cytotoxic agents, meanwhile, TTF was safe when given a single oral dose of 5000 mg/kg. However, caution is necessary in case of prolonged oral administration due to potential alterations of renal function at high doses (> 1000 mg/kg).

Flavanols from Tetrapleura tetraptera with cytotoxic activities.

Tetrapleura tetraptera is a medicinal plant used in East and West Africa to treat inflammation and related diseases. From the stem bark of the plant, three previously undescribed flavan-3-ol derivatives named (2R,3S)-3,3',5',7-tetrahydroxy-4'-methoxyflavane (1), (2R,3S)-3',5',7-trihydroxy-4'-methoxyflavane-3-O-ß-D-glucopyranoside (2), and (2R,3S,4S)-3,3',4,5',7-pentahydroxy-4'-methoxyflavane (3) were isolated with three known analogues. The structural elucidation of the compounds was performed based on NMR spectroscopy and HRMS data analyses. The absolute configurations around the stereogenic carbons were determined using Circular Dichroism (ECD) and density functional theory (DFT) calculations. The cytotoxicity of the isolated compounds was tested using resazurin reduction assay. Compound 1 was moderately active against both recalcitrant leukemia cell lines with IC50 values of 21.90 µM towards CCRF-CEM and 50.80 towards CEM/ADR5000. Similar level of activity was observed for compound 3 against CCRF-CEM cell line, IC50 = 35.50 µM. All the tested compounds were not cytotoxic compared with the standard drug, doxorubicin, with IC50 values of 0.0075 against CCRF-CEM and 24.30 µM against CEM/ADR5000.

Anti-trypanosomal and anthelminthic properties of ethanol and aqueous extracts of Tetrapleura tetraptera Taub.

Trypanosomosis and helminthosis, considered as part of neglected tropical diseases, are parasitic infections of public health importance, especially in Africa. Medicinal plants have been used in most parts of Africa, to treat these parasitic infections. The study aims to determine the anti-trypanosomal and anthelminthic properties of Tetrapleura tetraptera (fruit and stembark). The aqueous extracts of T. tetraptera fruit (TTFaq) and stembark (TTSaq), as well as ethanol extracts of T. tetraptera fruit (TTFe) and stembark (TTSe), were screened for their in vitro anti-trypanosomal and anthelminthic activities against T. b. brucei and Pheretima posthuma worms, respectively. Preliminary phytochemical screening of all extracts and gas chromatography-mass spectrometry (GC-MS) analysis of most active extracts were conducted. TTFaq exhibited anti-trypanosomal activity with IC50 of 18.18 µg/mL. TTSe and TTFe had moderate anti-trypanosomal activity with IC50 of 34.76 and 34.84 µg/mL, respectively. TTSaq had relatively low activity against the parasite with IC50 of 55.03 µg/mL. The SI of T. tetraptera extracts was between the range of 0.14-2.09. TTFaq showed dose-dependent activity causing paralysis and death of the adult worms at all concentrations. At the least concentration of 0.625 mg/mL, TTFaq induced paralysis and death after 101.88 ± 0.8 and 242.64 ± 0.38 min of exposure, respectively compared with the negative control (p < 0.0001). TTFe, TTSe and TTSaq caused paralysis of worms after 318.32 ± 0.74, 422.5 ± 0.72, 422.20 ± 0.55 min of exposure at minimum concentrations of 2.5, 10 and 5 mg/mL, respectively (p < 0.0001). However, no death was observed in worms treated with TTFe, TTSe and TTSaq at all test concentrations. In the presence of sub-minimal inhibitory concentration of the extracts, TTFaq potentiated the anthelminthic activity of albendazole whiles TTFe, TTSaq and TTSe inhibited the activity of albendazole. Phytochemical screening revealed the presence of saponins, triterpenoids, reducing sugars, flavonoids (absent in TTFe), steroids (absent in TTFaq) and tannins (absent in TTSe and TTFe) in the extracts. GC-MS revealed the presence of 9-octadecenamide and betulic acid in TTFaq. Hence, there was evidence provided here that Tetrapleura tetraptera may be effective. This gives credence to their folkloric use. However, further study might be necessary to ascertain safety use in both humans and animals.

Abatement of neurobehavioral and neurochemical dysfunctions in cerebral ischemia/reperfusion injury by Tetrapleura tetraptera fruit extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera Taub. (family Fabaceae), is generally found in the lowland forest of tropical Africa. Its leaves and fruits are traditionally used in West Africa for the management of brain disorders. AIM OF THE STUDY: This study evaluated the effect of Tetrapleura tetraptera methanol fruit extract (TT) on bilateral common carotid artery occlusion-induced cerebral ischemia/reperfusion (I/R) injury in male Wistar rats. MATERIALS AND METHODS: Rats pretreated with TT for 7 days before a 30 min bilateral common carotid artery occlusion and reperfusion for 24 h were assessed for neurobehavioural deficits. Cortical, striatal and hippocampal oxidative stress, pro-inflammatory events, electrolyte imbalance and neurochemical dysfunctions, as well as hippocampal histopathological alterations, were also evaluated. HPLC-DAD analysis was performed to identify likely compounds contributing to the bioactivity of the extract. RESULTS: TT reduced I/R-induced behavioral deficits and ameliorated I/R-induced oxidative stress by restoring reduced glutathione level, increasing catalase and superoxide dismutase activities, and also reducing both lipid peroxidation and xanthine oxidase activity in the brain. TT attenuated I/R-increased myeloperoxidase and lactate dehydrogenase activities as well as disturbances in Na+ and K+ levels. Alterations elicited by I/R in the activities of Na+/K+ ATPase, complex I, glutamine synthetase, acetylcholinesterase, and dopamine metabolism were abated by TT pretreatment. TT prevented I/R-induced histological changes in the hippocampus. HPLC-DAD analysis revealed the presence of aridanin, a marker compound for Tetrapleura tetraptera, and other phytochemicals. CONCLUSIONS: These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Cytotoxic phytochemicals from the crude extract of Tetrapleura tetraptera fruits towards multi-factorial drug resistant cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera is an African medicinal spice used in traditional medicine to treat several ailments including cancer. AIM OF THE STUDY: The present study was designed to evaluate the cytotoxicity of the dichloromethane-methanol (1:1) extract of the fruits of Tetrapleura tetraptera (TTF) and its constituents: (3R, 4S)-3,4-dimethyloxetan-2-one (1), luteolin (2), stigmasterol (4), 3-O-[6'-O-undecanoyl-ß-D-glucopyranosyl]stigmasterol (6), olean-12-en-3-ß-O-D-glucopyranoside (7), 3-O-ß-D-glucopyranosyl-(1 â†’ 6)-ß-D-glucopyranosylurs-12-en-28-oic acid (8), 3-O-ß-D-glucopyranosyl-(1 â†’ 3)-ß-D-glucopyranosyl-27-hydroxyolean-12-ene-28-oic acid (9), methyl-O-ß-D-glucopyranoside (10), ß-D-fructofuranosyl-(2 â†’ 1)-ß-D-glucopyranoside (11) towards a panel of cancer cell lines including MDR phenotypes. The cellular mode of induction of apoptosis by TTF and compound 7 was further investigated. MATERIALS AND METHODS: The resazurin reduction assay (RRA) was applied to determine the cytotoxicity of the studied samples. The cell cycle (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1) and reactive oxygen species (ROS; H2DCFH-DA) were measured by flow cytometry. Column chromatography was used for the purification of TTF, whilst nuclear magnetic resonance (NMR) spectroscopic analysis was applied for structural elucidation. RESULTS: The botanical, TTF and the phytochemicals, 2, 7, 8 and 9 as well as doxorubicin exerted cytotoxicity against 9 cancer cell lines including drug-sensitive and drug resistant phenotypes. TTF, compound 7 and doxorubicin were the most active samples, and displayed IC50 values ranging from 10.27 µg/mL (in CCRF-CEM leukemia cells) to 23.61 µg/mL (against HCT116 p53-/- colon adenocarcinoma cells) for TTF, from 4.76 µM (against CCRF-CEM cells) to 12.92 µM (against HepG2 hepatocarcinoma cells) for compound 7, and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin. TTF induced apoptosis in CCRF-CEM cells through MMP alteration and increased ROS production while compound 7 induced apoptosis mediated by caspases activation, MMP alteration and increased ROS production. CONCLUSION: Tetrapleura tetraptera and some of its constituents, mostly compound 7 are good cytotoxic natural products that should be explored in depth to develop new drugs to fight cancers.

Phenolic Compounds from Water-Ethanol Extracts of Tetrapleura tetraptera Produced in Cameroon, as Potential Protectors against In Vivo CCl4-Induced Liver Injuries.

BACKGROUND: Liver diseases are a global health problem. Medicinal plants are being increasingly used to manage a wide variety of diseases including liver disorders. The aim of this study was to investigate the antioxidant properties and hepatoprotective activity of polyphenolic extract from the fruits of Tetrapleura tetraptera (T. tetraptera). RESULTS: The extract of T. tetraptera was administered at doses of 50 mg/kg and 100 mg/kg for 07 per os to rats before the induction of hepatotoxicity with of 2 ml/kg of 1:1 (v/v) carbon tetrachloride (CCl4) and olive oil through intraperitoneal route. The in vitro antioxidant and radical scavenging properties of T. tetraptera were conducted by the FRAP method, the phosphomolybdate method, and the inhibition potential of DPPH, ABTS, OH, and NO radicals. The extraction yield of T. tetraptera was 19.35%. This extract contains polyphenols (273.48 mg CAE/g DM), flavonoids (5.2549 mg SE/g DM), and flavonols (1.615 mg SE/g DM). This extract showed in vitro antioxidant activity, an inhibitor power of various free radicals, and radical scavenging potential dose-dependent. The fifty-percent inhibitory concentration of the extract (IC50) for the studied radical varied from 28.16 to 136 µg/L. In rats treated with the extract of T. tetraptera, in a dose-dependent manner, the levels of hepatotoxicity markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) significantly increased while the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and the level of reduced glutathione (GHS) significantly increased compared to the control group. CONCLUSIONS: The extracts from the fruit of T. tetraptera demonstrate antioxidant activity and hepatoprotective effects.

Acute and sub-acute toxicity of the aqueous extract from the stem bark of Tetrapleura tetrapteura Taub. (Fabaceae) in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetrapteura Taub. is a leguminous multipurpose tree (Fabaceae) indigenous to tropical Africa. Fruits, seeds and stem bark infusions or decoctions of Tetrapleura tetrapteura Taub. are used to treat many diseases, such as gastric ulcer, rheumatism, malaria, hypertension and hyperlipidemia. AIM OF THE STUDY: This work was conducted to evaluate the acute and sub-acute toxicity of the aqueous extract of Tetrapleura tetrapteura Taub. (AETT) stem barks. MATERIALS AND METHODS: For the study of acute toxicity, single oral doses of 2000 mg/kg and 5000 mg/kg of AETT were administrated to male and female Balb/c mice, followed by observation of mice for 14 days. In the study of sub-acute toxicity, 48 albino wistar rats of both genders were randomly divided into six groups of 8 animals and they were daily and orally administrated for twenty eight days. The animal's test groups and satellite test group were administrated with the extract (AETT) at the doses of 100, 200 and 400 mg/kg and 400 mg/kg respectively. On the 29th day, the satellite group (control 2 and satellite 400 mg/kg) were observed during two more weeks. General behavior changes, mortality, body weight of animal, water and food intake were recorded during the study period. At the end of each treatment period, biochemical and hematological parameters were measured and histological examinations of liver and kidneys sections performed. RESULTS: Up to 5000 mg/kg single dose administration of AETT for fourteen days registered no death animal. In sub-acute study, no mortality was recorded in various experimental groups. Significant reductions in body weight, water and food intake were recorded in all treated animals. Relative weights of liver, kidneys, stomach, spleen, lungs, and heart of treated animals remained unchanged. Significant increases in the number of platelets as well as in serum ALAT level were recorded in rats, treated with 400 mg/kg of AETT. Female rat liver histology showed, at a higher dose of AETT, a slight congestion of portal vein. CONCLUSION: AETT is safe after therapeutic (200 mg/kg) or acute administration. Higher dose (400 mg/kg) administered for longer period showed signs of liver toxicity.

Schistosomiasis: Snail-vector control, molecular modelling and dynamic studies of bioactive N-acetylglycoside saponins from Tetrapleura tetraptera.

Schistosomiasis, a chronic neglected tropical disease caused by the Schistosoma spp. parasite, is associated with disabling patient symptoms. The new focus of the WHO roadmap on 'transmission control, wherever possible' offers drug development opportunities for intermediate-host control to prevent human-to-snail-to-human parasite transmission. Reports on the analysis of the impact of 'chemical-based mollusciciding' have concluded that constant application of molluscicides may contribute significantly towards the elimination of schistosomiasis in endemic areas. In South-Western Nigeria, Tetrapleura tetraptera is a tree whose fruit has been widely used in snail vector control. The presence of molluscicidal N-acetyl triterpene glycosides in the fruit has been reported. In this study, a bioactivity-directed fractionation of the fruit extract was performed to isolate the most potent molluscicidal saponin from the fruit. In an attempt to provide mechanistic insight into the observed activity, in silico screening was performed, profiling the molluscicidal N-acetyl triterpene glycosides reported from the fruit against two potential therapeutic targets in the mollusk used, NADH-ubiquinone oxidoreductase (NAD1) and retinoid X receptor. The docking predicted binary complexes of the saponins, which were subjected to explicit solvent conformational sampling from which patterns of structural stability were obtained. The binding energies alone did not account for the potency of the saponins indicating the influence of other factor like pharmacokinetic parameters. The study concluded that there is a preferential suitability of ND1's MWFE site for the rational design and development of novel molluscicidal agents.

Aqueous extracts of two tropical ethnobotanicals (Tetrapleura tetraptera and Quassia undulata) improved spatial and non-spatial working memories in scopolamine-induced amnesic rats: Influence of neuronal cholinergic and antioxidant systems.

BACKGROUND: Tetrapleura tetraptera (TT) and Quassia undulata (QU) are two predominant tropical ethnobotanicals with various medicinal values but are commonly used in folklore for the treatment of mental illness without justifiable mechanisms of action. AIM OF THE STUDY: To investigate the effects of aqueous extracts from TT fruits and QU leaves on the spatial and non-spatial working memory, antioxidant status and activities of neuronal marker enzymes of scopolamine-induced amnesic rats and thus, understand the possible mechanism of action of these plants. MATERIALS AND METHODS: Fifty-five albino rats were divided into eleven groups. Group I (normal rats) received normal saline (p.o), Group II-V (normal rats) administered with 50 and 300 mg/kg of each extract group VI (induced rats) received 2 mg/kg of scopolamine (i.p.), groups VII-X (induced rats) pretreated with 50 and 300 mg/kg of TT and QU extracts (p.o) before scopolamine administration, group XI (induced rats) treated with 2.5 mg/kg of donepezil. The treatment lasted for 14 days and amnesia was induced by a single dose of 2 mg/kg of scopolamine on the last day. Spatial (Y-maze) and non-spatial (novel objectect recoginiton test) working memories of the rats were tested. Thereafter, the animals were sacrificed and homogenates of isolated brain samples were assayed for cholinesterase activity and malondialdehyde (MDA) content. The phenolic characterisation of the samples was also carried out using HPLC-DAD chromatography. RESULTS: Administration of 2 mg/kg of scopolamine brought about a decrease in spatial and non-spatial memory indeces, increase in acetylcholinesterase and butyrylcholinesterase activities, as well as increased MDA content compared to the control. However, pretreatment with both extracts improved both spatial and non-spatial working memories and ameliorated the increased enzyme activities and MDA contents. Furthermore, the HPLC-DAD characterization of the extracts revealed the presence of p-coumaric acid, rutin, catechin, ellagic acid, quercetin, caffeic acid, chlorogenic acid and galic acid. CONCLUSION: The ability of the extracts to improved cognitive function and ameliorate impairment in cholinergic enzyme activities and antioxidant status in scopolamine-induced amnesic rats could help justify the possible neuroprotective properties of TT and QU and also explain possible mechanism of action of these ethnobotanicals as obtained in folklore medical practices.

Tetrapleura tetraptera spice attenuates high-carbohydrate, high-fat diet-induced obese and type 2 diabetic rats with metabolic syndrome features.

BACKGROUND: Tetrapleura tetraptera, a seasoning and nutritive spice is also used in western African folk medicine in the management of wide variety of diseases including diabetes, inflammation and hypertension. Flavonoids and saponins are some abundant secondary metabolic constituents in the fruits of this plant. This study aimed at evaluating the potential therapeutic action of the polyphenol-rich hydroethanolic extract (HET) of this fruit in experimentally induced obese and type 2 diabetic rats (T2DM) with characteristic metabolic syndrome (MetS). METHODS: MetS was induced in rats by high-carbohydrate, high-fat diet and administration of low-dose streptozotocin. Then different oral doses of HET (200 and 400 mg/kg) were administered to T2DM rats for 28 days. A standard antidiabetic drug, metformin (300 mg/kg), was used for comparison. The body weight, systolic blood pressure, oxidative stress and metabolic parameters were then assessed to evaluate the effect of HET on MetS. RESULTS: HET reduced weight gain, fasting blood glucose and plasma insulin levels as well as homeostasis model assessment of insulin resistance (HOMA-IR) and alleviated obesity and T2DM associated oxidative stress and hypertension in rats. Moreover, a significantly hypolipidemic property and an attenuation of liver injury and tissue steatosis was observed after HET administration. HET further demonstrated its anti-inflammation effect via down regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), leptin and an increase in adiponectin. The HET exhibited dose-dependent effects which were comparable to that of metformin. CONCLUSIONS: The present study thereby demonstrates the anti-insulin resistance, antilipidemic, anti-obesity, hypotensive and anti-inflammatory properties of HET; hence it has the potential to be further developed for the management of MetS such as obesity, T2DM and hypertension.

Effects of ethanolic extract of Tetrapleura tetraptera fruit on serum lipid profile and kidney function in male Dutch-white rabbits.

BACKGROUND: Tetrapleura tetraptera fruit is widely used in Nigeria as a spice and for treatment of various medical ailments. Reports indicate that feeding of extracts to animals produced some toxic effects and pathological lesions in some organs. OBJECTIVE: This study was designed to investigate the effects of 10 days oral administration of the ethanolic extract of Tetrapleura tetraptera (TTE) on the lipid profile and kidney function in male rabbits. METHODS: Twenty healthy, acclimatized male rabbits weighing 1.4 - 1.6 kg were randomly divided into four groups. Group 1 served as control and received only water while groups 2, 3 and 4 were administered 50, 100 and 150 mg/kg bodyweight of TTE respectively. Fasting serum from all groups were analyzed for lipid profile and kidney function parameters using standard protocols. Data were analyzed using student's t-test and ANOVA. RESULTS: Tetrapleura tetraptera extract elicited reduction in serum triacylglycerols, elevation of LDL-cholesterol and alteration of kidney function parameters in male rabbits. CONCLUSION: Ethanolic extract of Tetrapleura tetraptera may predispose to hypertension and cardiovascular diseases.

Essential oil composition, antibacterial activity and toxicity of the leaves of Tetrapleura tetraptera (Schum. & Thonn.) taubert from Nigeria.

The composition of the essential oil of the leaves of Tetrapleura tetraptera (Schum. & Thonn.) Taubert. from Nigeria were analyzed by GC/MS. Forty-one compounds representing 89.5% of the essential oil were characterized. The essential oil was dominated by 1,8-cineole (19.4%), 6,10,14-trimethyl-2-pentadecanone (13.6%), phytol (9.1%), alpha-pinene (8.1%) and geranylacetone (6.7%). The oil exhibited moderate toxicity in the brine shrimp lethality assay (117.5 microg/mL), and displayed weak antibacterial activity against Bacillus subtilis.

Tetrapterosides A and B, two new oleanane-type saponins from Tetrapleura tetraptera.

From the stem bark of Tetrapleura tetraptera, two new oleanane-type saponins, tetrapteroside A 3-O-{6-O-[(2E,6S)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl]-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1 --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl}-3,27-dihydroxyoleanolic acid (1), and tetrapteroside B 3-O-{ beta-D-glucopyranosyl-(1 --> 2)-6-O-[(E)-feruloyl]-beta-D-glucopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1 --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl}-3,27-dihydroxyoleanolic acid (2), were isolated. Further extractions from the roots led to the isolation of four known oleanane-type saponins. Their structures were elucidated by the combination of mass spectrometry (MS), one and two-dimensional NMR experiments.

Antimalaria activity of ethanolic extract of Tetrapleura tetraptera fruit.

The in vivo antiplasmodial activity of the ethanol fruit extract of Tetrapleura tetraptera used as spice and in the treatment of various ailment in Niger Delta region of Nigeria was evaluated in Plasmodium berghei infected mice. Tetrapleura tetraptera (300-900 mg/kg day) exhibited significant (P < 0.05) blood schizonticidal activity both in 4-day early infection test and in established infection with a considerable mean survival time comparable to that of the standard drug, chloroquine, 5 mg/kg day. The fruit extract possesses significant (P < 0.05) antiplasmodial activity with may have contributed to the immune status of the Nigerians against malaria in addition to its nutritive value.

Analgesic and anticonvulsant properties of Tetrapleura tetraptera (Taub) (Fabaceae) fruit aqueous extract in mice.

Previous studies in our laboratories and elsewhere have shown that the fruit of Tetrapleura tetraptera (Taub) (family: Fabaceae) is widely used in African traditional medicine for the management and/or control of an array of human ailments, including schistosomiasis, asthma, epilepsy, hypertension and so on. The present study was designed to investigate the analgesic and anticonvulsant effects of Tetrapleura tetraptera (Taub) fruit aqueous extract (TTE) in mice. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), phenobarbitone (20 mg/kg i.p.) and diazepam (0.5 mg/kg i.p.) were used, respectively, as reference analgesic and anticonvulsant agents for comparison. T. tetraptera fruit aqueous extract (TTE, 50-800 mg/kg i.p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced pain in mice. Like the standard anticonvulsant agents (phenobarbitone and diazepam) used, T. tetraptera fruit aqueous extract (TTE, 50-800 mg/kg i.p.) significantly (p < 0.05-0.001) delayed the onset of, and antagonized, pentylenetetrazole (PTZ)-induced seizures. Aqueous extract of the fruit (TTE, 50-800 mg/kg i.p.) also profoundly antagonized picrotoxin (PCT)-induced seizures, but only partially and weakly antagonized bicuculline (BCL)-induced seizures. However, the results of this experimental animal study indicate that Tetrapleura tetraptera (Taub) fruit aqueous extract (TTE) possesses analgesic and anticonvulsant properties. These findings lend pharmacological support to the suggested folkloric uses of the plant's fruit in the management and/or control of painful, arthritic inflammatory conditions, as well as for the management and/or control of epilepsy and childhood convulsions in some tropical African countries.