Biflavonoid Methylchamaejasmin and Khaya grandifoliola Extract Inhibit NLRP3 Inflammasome in THP-1 Cell Model of Neuroinflammation.

Neuroinflammation is a common hallmark of Alzheimer's disease (AD), with NLRP3 inflammasome proven to be activated in microglia of AD patients' brains. In this study, a newly isolated biflavonoid (7,7'-di-O-methylchamaejasmin/M8) and a crude extract of the plant Khaya grandifoliola (KG) were investigated for their inhibitory effect on inflammasome activation. In preliminary experiments, M8 and KG showed no cytotoxicity on human macrophage-like differentiated THP-1 cells and exhibited anti-inflammatory inhibition of nitric oxide produced following lipopolysaccharide stimulation. Furthermore, M8 and KG blocked IL-1ß and IL-18 production by reducing NLRP3 inflammasome components including NFκB, NLRP3, Caspase-1, pro-IL-1ß, and pro-IL-18 at the mRNA and protein levels. Regarding the formation of ASC (apoptosis-associated speck-like protein containing a CARD) specks during inflammasome activation, the size and fluorescent intensity of the existing specks were unchanged across all treatment conditions. However, M8 and KG treatments were shown to prevent further speck formation. In addition, experiments on amyloid ß phagocytosis showed that M8 and KG pretreatments can restore the phagocytic activity of THP-1 cells, which was impaired following inflammasome activation. Altogether, our findings describe for the first time a promising role of biflavonoids and KG extract in preventing inflammasome activation and protecting against neuroinflammation, a key factor in AD development.

Performance and CO2 emission of a single cylinder compression ignition engine powered by Khaya senegalensis non-edible seeds fuel blends.

This work aimed at investigating blends of Khaya senegalensis biodiesel in a compression ignition engine, attempting to improve engine performance and reduce CO2 emission compared with conventional diesel. Analysis of System (ANSYS) was used to predict in-cylinder behavior of the fuel. ANSYS SpaceClaim generated the geometric model on which 5° sector and mesh refinement was on ANSYS Internal Combustion Engine Modeler (ICEM). Computational domain of interest lies within the compression and expansion strokes. Experimental validation followed: 5% biodiesel, 95% diesel (B5); 15% biodiesel, 85% diesel (B15); 25% biodiesel, 75% diesel (B25); pure diesel (D100); pure biodiesel (B100) in volume proportions. B15 has the highest brake mean effective pressure (BMEP) of 4 bar as load increases. An experimental and numerical comparison reveals pressure declination against speed increment. Ignition temperature fluctuated between 799.76 and 806.256 K for D100 and 760.73-790.62 K for B100 within 1800-2800 rpm speed limit prediction. Power and brake thermal efficiency (BTE) had parallel load increment with all blends. CO2 emission on increasing load conditions were 47.01%, 8.07%, 21.72% and 6.06% for B5, B15, B25, and B100 respectively lower than D100. Pressure and temperature contours gave proper combustion predicted behaviors. All blends possess replaceable performance potential for D100 however, B5 offers better reliable potentials.

Phytochemical and anticonvulsant screening of three medicinal plants used in the treatment of epilepsy in the south-western part of Nigeria

The burden of epilepsy in developing countries made medicinal plants like Xylopia aethiopica fruit; Khaya grandifoliola, Alstonia boonei etc an alternative source in epilepsy management in the south-western part of Nigeria. The aim of the study was to provide pharmacological rationale for the ethnomedicinal use of the plants in epilepsy management. The oral medial lethal dose of methanol stem bark extracts of Alstonia boonei (MEAB) and Khaya grandifoliola (MEKG) and methanol fruit extract of Xylopia aethiopica (MEXAF) were done in accordance with the Organization for Economic Cooperation Development guideline. Quantitative and qualitative phytochemical profiling of the extracts was done. Anticonvulsant screening was carried out on the extracts (doses: 75, 150 and 300 mg/kg) using the pentylenetetrazole (PTZ)-induced seizure and maximum electroshock tests (MEST). Results showed that the MEXAF has the highest amount of phytochemicals except for saponins in MEKG; and MEAB with the least amount (but higher alkaloid) than MEKG. The TLC showed different bands of spots of the extracts. In the PTZ test, MEXAF showed 100 % protection against mortality at 300 mg/kg; MEAB with 66.67 % protection at 75 mg/kg and MEKG 0 % protection. MEAB, MEKG and MEXAF nonsignificantly increased the onset of seizure and latency to death. In the MEST, MEXAF, MEKG and MEAB at 75 mg/kg protected 50, 33.3 and 16.67% of the animals against tonic hind limb extension respectively and nonsignificantly (p˃0.05) decreased the recovery time at a dose of 75 mg/kg. It was concluded that the extracts possess anticonvulsant activities hence, the pharmacological credence for the ethnomedicinal use of these plants in treating epilepsy.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

Mexicanolide limonoids from the seeds of Khaya ivorensis with antimicrobial activity.

The methanol extract of the seeds of Khaya ivorensis afforded two new mexicanolide limonoids, ivorensines A and B (1 and 2), together with one known compound, ruageanin D (3). The structures of the isolated compounds were established based on 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. As a result, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 50 µg/ml.

Evaluating Khaya senegalensis for Dipeptidyl Peptidase-IV Inhibition Using in Vitro Analysis and Molecular Dynamic Simulation of Identified Bioactive Compounds.

The dipeptidyl peptidase-IV (DPP-IV) inhibitory activity of Khaya senegalensis extracts was evaluated. The DPP-IV from a rat kidney was purified to a purification fold of 2.3. Among extracts from K. senegalensis, the hexane extract had the best DPP-IV inhibitory activity, with IC50 value of 1.56±0.61 µg/mL and was fractionated to eleven fractions (A-K). Fraction I had the best DPP-IV inhibition via uncompetitive pattern. GC-MS analysis of fraction I showed that the major bioactive compounds were 3-amino-3-hydroxyimino-N-phenylpropanamide (1) and 11-(2-cyclopenten-1-yl)undecanoic acid (2), with good binding affinities toward DPP-IV, based on molecular docking,. They were then subjected to molecular dynamic simulation using WEBGRO and utilizing a GROMACS system for 100 ns. The 3-amino-3-hydroxyimino-N-phenylpropanamide-DPP-IV complex was more stable and compact than the other complex. K. senegalensis contains compounds like 1 that might be used for the design of new DPP-IV inhibitors.

Hydro-ethanolic extract of Khaya grandifoliola attenuates heavy metals-induced hepato-renal injury in rats by reducing oxidative stress and metals-bioaccumulation.

People living in developing countries are exposed to hepato-renal injuries induced by heavy metals like lead (Pb), cadmium (Cd), and mercury (Hg) since drinking water supplied is often polluted with a high concentration of those metals. Accordingly, it is necessary to search for antidotes against heavy metals poisoning. Hence, medicinal plants bearing anti-hepatotoxic properties represent a credible option; and such plant is Khaya grandifoliola. However, there is a paucity of knowledge regarding its protective effect on heavy metals-induced hepato-renal toxicity. Thus, this study was designed to assess the protective effect of the hydro-ethanolic stem bark extract of K. grandifoliola (HKG) against hepato-renal injuries induced by chronic consumption of drinking water containing high contents of Pb, Cd, and Hg; in addition to the investigation of the chemical antioxidant properties of HKG. For the antioxidant assays, HKG was tested as a potential inhibitor of lipid peroxidation, reducer of ferric and phosphomolybdenum, and scavenger of hydroxyl and 2,2-Diphenyl-Picryl-Hydrazyl radicals. Its protective effects were evaluated by daily co-treating rats with heavy metals solution (10 mL/kg b.w) containing 0.9, 0.58, and 1.13 ppm respectively for Pb, Cd and Hg and HKG (25 or 100 mg/kg b.w) for five consecutive months; and biochemical parameters associated to liver and kidneys functions, oxidative stress and metals bioaccumulation were assessed. HKG displayed a strong antioxidant capacity (IC50/EC50 range 3.95-17.17 µg/mL) correlated to its polyphenols content and comparable to that of Ascorbic acid. Serum levels of alkaline phosphatase, alanine/aspartate aminotransferase, and creatinine; renal and hepatic content of Cd and Pb, malondialdehyde and glutathione, activities of superoxide dismutase and catalase showed the protective effect of HKG, further evidenced by histopathological analysis. Taking together, these results demonstrated that HKG alleviates heavy metals-induced hepato-renal injuries in rats by reducing oxidative stress and metals-bioaccumulation.

Khaya grandifoliola active fraction as a source of therapeutic compounds for Alzheimer's disease treatment: In silico validation of identified compounds.

Overproduction of Nitric oxide (NO) and many other pro-inflammatory mediators are responsible for many pathological disorders in humans, including Alzheimer's disease (AD). In this study, active fractions isolated from Khaya grandifoliola (Kg) were screened for their inhibitory activities against NO production in lipopolysaccharide (LPS)-activated microglia. Among the 5 fractions tested, Kg25 was the most active and showed potent inhibitory activity towards NO production. The fraction further showed inhibitory effect on iNOS's mRNA expression and other major pro-inflammatory cytokines including TNFα and IL1-ß. Study of the effect of Kg25 on p38MAPKinase and JNK3 showed that the fraction inhibits these signaling pathways known to be involved in cell inflammatory pathways. These observations were confirmed at the protein level with Kg25 inhibiting iNOS and p38MAPK protein expressions in N9 cells. Analysis of Kg25 composition by HPLC identified 3 main compounds, namely: 6 phenyl, 4-(1`oxyehylphenyl) hexane, Carbamic acid, (4-methly-1-phenyl)-1, phenyl, and Benzene, 1 1`-(oxydiethylidene) bis. The above mentionned compounds were further analyzed for their bioactivity against the p38MAPKinase and iNOS receptors using molecular docking. MolDock results showed that 1-phenylethyl N-(4-methylphenyl)carbamate (compound 2) possesses the highest binding affinity (for iNOS); and 1-(1-phenylethoxy)ethylbenzene (compound 3) (for pMAPK) respectively and both compounds interact well with the active site residues. Hence, these compounds could be considered as scaffolds for further development of lead- drugs targeting neuroinflammation in AD.

An aqueous extract of Khaya senegalensis (Desv.) A. Juss. (Meliaceae) prevents seizures and reduces anxiety in kainate-treated rats: modulation of GABA neurotransmission, oxidative stress, and neuronal loss in the hippocampus.

Ethnopharmacological relevance: Temporal lobe epilepsy is the most common form of drug-resistant epilepsy. Therefore, medicinal plants provide an alternative source for the discovery of new antiepileptic drugs. Aim of the study: This study was aimed at investigating the antiepileptic- and anxiolytic-like effects of an aqueous extract of Khaya senegalensis (K. senegalensis) in kainate-treated rats. Methods: Seventy-two rats received a single dose of kainate (12 mg/kg) intraperitoneally. Those that exhibited two hours of status epilepticus were selected and monitored for the first spontaneous seizure. Then, animals that developed seizures were divided into 6 groups of 8 rats each and treated twice daily for 14 days as follows: negative control group received per os (p.o.) distilled water (10 ml/kg); two positive control groups received either sodium valproate (300 mg/kg, p.o.) or phenobarbital (20 mg/kg, p.o.); and three test groups received different doses of the extract (50, 100, and 200 mg/kg, p.o.). In addition, a group of 8 normal rats (normal control group) received distilled water (10 ml/kg, p.o.). During the treatment period, the animals were video-monitored 12 h/day for behavioral seizures. At the end of the treatment period, animals were subjected to elevated plus-maze and open field tests. Thereafter, rats were euthanized for the analysis of γ-aminobutyric acid (GABA) concentration, oxidative stress status, and neuronal loss in the hippocampus. Results: The aqueous extract of K. senegalensis significantly reduced spontaneous recurrent seizures (generalized tonic-clonic seizures) and anxiety-like behavior compared to the negative control group. These effects were more marked than those of sodium valproate or phenobarbital. Furthermore, the extract significantly increased GABA concentration, alleviated oxidative stress, and mitigated neuronal loss in the dentate gyrus of the hippocampus. Conclusion: These findings suggest that the aqueous extract of K. senegalensis possesses antiepileptic- and anxiolytic-like effects. These effects were greater than those of sodium valproate or phenobarbital, standard antiepileptic drugs. Furthermore, these effects are accompanied by neuromodulatory and antioxidant activities that may be related to their behavioral effects. These data justify further studies to identify the bioactive molecules present in the extract for possible future therapeutic development and to unravel their mechanisms of action.

Antimicrobial mexicanolide limonoids from the seeds of Khaya senegalensis.

Three new mexicanolide limonoids were obtained from the 90% ethanol extract of the seeds of Khaya senegalensis. Their structures were elucidated as senegalenines A-C (1-3) by analysing their 1D/2D NMR and MS spectroscopic analysis. In addition, the isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. Consequently, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 40 µg/ml.

Annona muricata Linn and Khaya grandifoliola C.DC. Reduce Oxidative Stress In Vitro and Ameliorate Plasmodium berghei-Induced Parasitemia and Cytokines in BALB/c Mice.

BACKGROUND: Annona muricata and Khaya grandifoliola are ethnomedicinally used for the treatment of malaria and have been experimentally shown to have an anti-plasmodial effect, but the mechanisms involved are not fully understood. This study investigated the effect of the ethanol extracts of their leaves on parasitemia, radical scavenging and cytokines in Plasmodium berghei ANKA-infected BALB/c mice. METHODS: BALB/c mice were infected with P. berghei and treated with chloroquine, A. muricata or K. grandifoliola extract for 4 days. The percentage of parasitemia and the level of cytokine expression were determined after treatment. Trace element, phytochemical and nitric oxide (NO) scavenging activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging properties assays were done to study the antioxidant effects of AN and KG in vitro. RESULTS: P. berghei consistently increased parasitemia in BALB/c mice. The tested doses (100-, 200-, and 400 mg/kg) of A. muricata and K. grandifoliola attenuated the P. berghei-induced elevation of parasitemia and cytokines (TNF-α, IL-5, and IL-6) in vivo during the experimental period, though not as much as chloroquine. Moreover, both extracts scavenged the DPPH and NO radicals, though A. muricata had more anti-oxidant effect than K. grandifoliola in-vitro. CONCLUSION: The ethanol extracts of A. muricata and K. grandifoliola reduce parasitemia in P. berghei-treated mice BALB/c by scavenging free radicals and reducing cytokines, though the extracts were not as effective as chloroquine.

Argyrotoxins A-C, a trisubstituted dihydroisobenzofuranone, a tetrasubstituted 2-hydroxyethylbenzamide and a tetrasubstitutedphenyl trisubstitutedbutyl ether produced by Alternaria argyroxiphii, the causal agent of leaf spot on African mahogany trees (Khaya senegalensis).

Three previously undescribed metabolites named argyrotoxins A-C, were isolated, together with the well known porritoxinol, its closely related phthalide, a phthalide derivative, zinniol, alternariol and its 4-methyl ether from Alternaria argyroxiphii E.G. Simmons & Aragaki, the causal agent of leaf spot on African mahogany trees, Khaya senegalensis A. Juss. (Meliaceae). The known compounds were identified comparing their physical and spectroscopic properties to those previously reported in literature. Argyrotoxins A-C were characterized essentially by NMR (1H, 13C, COSY, HSQC, HMBC and NOESY NMR spectra) and HRESIMS spectra as 4-(7-methoxy-6-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yloxy)-2-methyl-butyric acid, 5-but-2-enyloxy-N-(2-hydroxyethyl)-2-hydroxymethyl-3-methoxy-4-methyl-benzamide and 1-(5-(hydroxymethyl)-3-methoxy-4-(methoxymethyl)-2-methylphenoxy)-3-methylbutane-2,3-diol, respectively. The absolute configuration of argyrotoxin A was determined through electronic circular dichroism, by applying the biphenyl chiroptical probe approach. The phytoxicity of all metabolites isolated was evaluated by leaf puncture assay at concentration of 1 mg/mL. Zinniol proved to be the most active compound causing necrotic lesions on young leaves of Hedera elix L., Phaseolus vulgaris L. and Quercus ilex L. Argirotoxins A and B were found active, to a minor extent, on Phaseolus vulgaris L. leaves, while porritoxinol exhibited activity on holm oak leaves. The other secondary metabolites herein reported for A. argyroxiphii were inactive.

Inhibitory activity of limonoids from Khaya grandifoliola C.DC (Meliaceae) against hepatitis C virus infection in vitro.

OBJECTIVE: A fraction from Khaya grandifoliola has recently been shown to inhibit hepatitis C virus (HCV) infection and three limonoids (17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and 7-deacetoxy-7R-hydroxygedunin) were purified from this fraction. The present study aimed at assessing the inhibitory effect of these limonoids on HCV using cell-culture derived HCV (HCVcc) system. MATERIALS AND METHODS: Cytotoxic effects of the limonoids on Huh7.5 cells were assessed by MTT assay. Huh7.5 cells were transfected with RNA transcripts of the plasmid Jc1/GLuc2a, carrying a Gaussia luciferase reporter gene to rescue the HCVcc particles which were used to infect naïve cells in the presence or absence of the studied limonoids during 72 hr. Infection and replication rates were monitored by luciferase reporter assay and immunofluorescence assay (IFA) while cellular gene expression was analyzed by western blot, respectively. RESULTS: The limonoids inhibited HCV infection mostly by targeting entry and replication stage. Their inhibitory effect on entry step, comparable to that of anti-CD81 antibody, was related to the blocking of CD81 receptor. In the replication step, the limonoids decreased the expression of NS5B similar to danoprevir. These compounds also significantly decreased but up-regulated the expression of Class-III phosphatidylinositol 4-kinase alpha and 2',5'-oligoadenylate synthase-3, respectively. CONCLUSION: The present findings suggest that limonoids from K. grandifoliola are potential anti-HCV agents and may offer an advantage in the treatment of HCV infection.

Ameliorative effects of the aqueous extract of Khaya anthotheca (Welw.) C.DC (Meliaceae) in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical enquiries have revealed that Khaya anthotheca (Welw.) C.DC (Meliaceae) has anxiolytic properties and is used to alleviate vaginal dryness in postmenopausal women in Cameroon. The aim of this study was to evaluate the ameliorative effects of the aqueous extract of K. anthotheca in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice. MATERIAL AND METHODS: Forty neonatal female mice were used in this study. All animals received vanadium (3 mg/kg BW/72 h, by lactation and i.p.) for 20 weeks except the Control group. At 16 weeks old, mice were divided into 5 groups (n = 8): Control group received distilled water; V-group received vanadium (V) (3 mg/kg BW every 72 h i.p.), V + Vit E group received vitamin E (500 mg/kg BW/72 h) and vanadium (V) (3 mg/kg BW/72 h i.p, simultaneously). V + KA 125 and V + KA 250 groups received K. anthotheca extract at the doses of 125 and 250 mg/kg BW/day respectively and vanadium (V) (3 mg/kg BW/72 h i.p, simultaneously).The treatment was done per os at 10 mL/kg of volume of administration for 4 weeks. To evalute anxiolytic effects and spatial working memory improved by the extract in mice, the elevated open space test and Y maze test were used respectively. After sacrifice, brains were harvested and pathologies were assessed using cresyl violet stainning and immunohistochemistry (GFAP, Iba-1 and MBP), while pathologies in the ovaries were assessed using immunohistochemistry (Collagen type 1) and H&E stainning. RESULTS: Results in the three sessions of elevated open space test showed that vanadium exposure resulted in a significant (p < 0.05; p < 0.01) increase of the latency of first entry in the slopes and a significant (p < 0.05; p < 0.01; p < 0.001) decrease of the time spent and number of entries in the slopes however, Khaya anthotheca treatment induced a significant (p < 0.05; p < 0.01) decrease of the latency of first entry in the slopes and a significant (p < 0.05; p < 0.01) increase of the time spent and number of entries in the slopes. In the Y maze test, vanadium exposure resulted in a significant decrease (p < 0.01) in the percentage of correct alternation, K. anthotheca extract at the dose of 250 mg/kg BW however induced a significant (p < 0.05) increase of this percentage of correct spontaneous alternation. In the brain, degeneration induced by vanadium exposure was marked by an increase of GFAP-immunoreactive cells, microgliosis and demyelination. The treatment with Khaya anthotheca extract at the dose of 250 mg/kg BW resulted in the preservation of cellular integrity in the same anatomical regions with reduced astroglial and microglial activation and prevented demyelination. In addition, vanadium exposure decreased Collagen type 1 expression in the ovaries and induced a deterioration of tertiary follicle. Khaya anthotheca treatment at the dose of 250 mg/kg BW induced an increase of expression of Collagen type 1 and alleviated deterioration of the microarchitecture of tertiary follicle induced by vanadium. CONCLUSION: These effects induced by K. anthotheca extract could justify the traditional use of this plant in Cameroonian traditional medicine to manage anxiety. Therefore, to minimise vanadium induced toxicity, the plant should be given more emphasis as a candidate in developing a modern phytodrug.

The formation of interlocked grain in African mahogany (Khaya spp.) analysed by X-ray computed microtomography.

Interlocked grain occurs when the orientation of xylem fibres oscillates, alternating between left- and right-handed spirals in successive wood layers. The cellular mechanisms giving rise to interlocked grain, thought to involve the slow rotation of fusiform initials within the vascular cambium, remain unclear. We suggest that observations of wood structure at the cellular level, but over large areas, might reveal these mechanisms. We assayed timber from several commercially important tropical angiosperms from the genus Khaya (African mahogany) that exhibit interlocked grain using X-ray computed microtomography followed by orthogonal slicing and image processing in ImageJ. Reconstructed tangential longitudinal sections were processed with the ImageJ directionality plug-in to directly measure fibre orientation and showed grain deviations of more than 10° from vertical in both left- and right-handed directions. Grain changed at locally constant rates, separated by locations where the direction of grain change sharply reversed. Image thresholding and segmentation conducted on reconstructed cross sections allowed the identification of vessels and measurement of their location, with vessel orientations then calculated in Matlab and, independently, in recalculated tangential longitudinal sections with the directionality plug-in. Vessel orientations varied more than fibre orientations, and on average deviated further from vertical than fibres at the locations where the direction of grain change reversed. Moreover, the reversal location for vessels was shifted ~400 µm towards the pith compared with the fibres, despite both cell types arising from the same fusiform initials within the vascular cambium. We propose a simple model to explain these distinct grain patterns. Were an auxin signal to control both the reorientation of cambial initials, as well as coordinating the end-on-end differentiation and linkage of xylem vessel elements, then it would be possible for fibres and vessels to run at subtly different angles, and to show different grain reversal locations.

Bioactivity assays, chemical characterization, ADMET predictions and network analysis of Khaya senegalensis A. Juss (Meliaceae) extracts.

Khaya senegalensis A. Juss (Meliaceae) is a popular medicinal plant, widely used in the management of various ailments in the African traditional medicine. This study attempts to investigate into the different extraction methods (homogenizer-assisted extraction (HAE), maceration (MAC), infusion and Soxhlet (SE) extraction) on the pharmacological properties and chemical profiles of K. senegalensis. Antioxidant properties and inhibitory potential against key enzymes were assessed and bioinformatics analysis was conducted on selected limonoids to predict putative pharmacokinetics and protein targets underlying the pharmacological effects. Overall, the leaf extracts showed notable flavonoid (20.59-104.43 mg RE/g) content and the stem barks extracts displayed the highest total phenolic (87.69-46.28 mg GAE/g), phenolic acid (62.96-107.22 mg CE/g), flavanol (3.60-135.40 mg CAE/g) contents. All extracts showed remarkable antioxidant activities, with the MAC-Water leaf extract being most active in all the assays. Regarding stem bark, the MAC-MeOH extract exerted the highest free radical scavenging abilities, while HAE and MAC extracts were better sources of reducing agent and metal chelators. The HAE-MeOH, MAC-Water, and SE extracts showed noteworthy inhibitory activity against AChE, BChE (only stem barks), tyrosinase and α-glucosidase (only stem barks). All extracts displayed moderate inhibitory activities against α-amylase. The bioinformatics approach showed that khayanoside A and C interacted with multiple isoforms of metalloproteinase, while humilin B and khayanone interacted with opioid receptors. To sum up, the chemical profiles and biological activities of K. senegalensis were closely dependent on the extraction methods. Results amassed from this study showed that K. senegalensis is a potent source of bioactive compounds which could be explored as a functional food.

Furan fragment isomerized andirobin-type limonoids from the stem barks of Khaya senegalensis.

A new andirobin-type limonoid with modified furan ring, khaysenelide K (1), together with a known analogue (2), was isolated from the stem barks of Khaya senegalensis. The structure and absolute configuration of 1 were elucidated by a combination of 1D and 2D NMR, HRESIMS, and single-crystal X-ray diffraction using mirror Cu-Kα radiation. Compound 1 showed moderate NO inhibitory activity in LPS-activated RAW 264.7 macrophages with IC50 value of 27.74 ± 0.68 µM.[Formula: see text].

Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis.

Background Concomitant exposure to environmental/occupational toxicants such as aflatoxin B1 (AFB1) and arsenic in some regions of the world has been well reported. Therefore, this calls for the assessment of the efficacy of agents such as phytochemicals, which are already known for their ethno-medicinal uses in prophylaxis/remediation. We investigated the possible cytotoxic bio-interactions between AFB1 and sodium arsenite (SA) in urinary bladder cells. We also assessed the cytoprotective effects of curcumin and the ethanol stem bark extract of Khaya senegalensis (K2S). Methods The cells were exposed to graded levels of AFB1, SA, curcumin, and K2S for 24, 48, and 72 h. Subsequently, using optimum toxic concentrations of AFB1 and SA, respectively, the influence of non-toxic levels of curcumin and/or K2S was tested on exposure of the cells to AFB1 and/or SA. Hoechst 33342/propidium iodide staining technique was used to determine the end-points due to cytotoxicity with changes in adenosine triphosphate (ATP) levels determined using Promega's CellTiter-Glo luminescent assay. Results Co-treatment of the cells with AFB1 and SA resulted in synergy in cytotoxic effects. Cytotoxicity was reduced by 3.5- and 2.9-fold by pre-treatment of the cells with curcumin and K2S before treatment with AFB1, while post-treatment resulted in 1.1- and 2.6-fold reduction, respectively. Pre-exposure of the cells with curcumin and K2S before treatment with SA ameliorated cytotoxicity by 3.8- and 3.0-fold, but post-treatment caused a 1.2- and 1.3-fold reduction, respectively. Conclusions Pre-treatment of the cells with either curcumin or K2S exhibited cytoprotective effects by ameliorating AFB1- and SA-induced cytotoxicity with inferred tendencies to prevent carcinogenesis.

Anticoccidial effects of Khaya senegalensis aqueous stem bark extract on broiler chickens experimentally infected with Eimeria species.

Graded concentrations (200, 400 and 800 mg/kg) of the aqueous stem bark extract of Khaya senegalensis was evaluated for its therapeutic efficacy against experimentally induced coccidiosis in broiler chicken. The phytochemical analysis shows the presence of tannins, saponins, cardiac glycosides and steroids. There was significant reduction in oocyst count across the groups in a graded dose manner with 800 mg/kg being the most efficacious dose. There was also weight gain across the treatment groups with immuno-modulatory and erythropoetic activities observed. Also, a significant (p < 0.05) graded dose-dependent reduction in the oocyst count in the treatment groups. A significant (p < 0.05) increase in mean weight gain was also recorded across the experimental groups except the negative control. The haematology also showed a dose-dependent increase in red blood cells, haemoglobin and packed cell volume of the treatment groups. The extract had no significant difference (p > 0.05) on the white blood cells, but a slight decrease in the white blood cells and heterophil counts was observed at 400 mg/kg. Furthermore, the aspartate amino transaminase level showed a significant difference (p < 0.05). Fluctuating levels of other serum biochemical parameters such as total protein, albumin and potassium were observed. No significant difference (p > 0.05) in the sodium concentration was observed. In addition, oxidative stress biomarkers such as catalase significantly increased (p < 0.05) in all the experimental groups in addition to the concomitant increase in reduced gluthathione (GSH) and superoxide dismutase (SOD) levels. Conclusively, the aqueous extract of K. senegalensis was effective in the management of coccidiosis thus supporting its folkloric use.

Transpiration and growth of young African mahogany plants subject to different water regimes.

Timber production has been prominent in the Brazil scenario to minimize deforestation. Thus, technical information is necessary to define the productive process of the African mahogany in the Midwest region of Brazil, especially with regard to its hydric parameters. Recent studies, reported in the literature, have shown that irrigation improves the performance of young African mahogany plants in the field. Sap flow measurement can be used to estimate transpiration of perennial plants and to determine their water demand. This study evaluated the influence of two water regimes on the transpiration and growth of an African mahogany forest after irrigation has ceased. Moreover, this study also characterizes the seasonal patterns of transpiration and growth of African mahogany under these conditions. African mahogany plants with 2.5 years of age were cultivated in Bonfinopolis-GO and evaluated for 2 years. Treatments were IT-irrigated until 2 years of age-and NIT-non-irrigated. Plant height (PH), breast height diameter (DBH), trunk volume (TRV), leaf area (LA), leaf dry matter (LDM), and transpiration (T) were monitored by heat dissipation probe (HDP) between Oct/2014 and Oct/2015. Higher growth in LA, DBH, and LDM were observed in IT. However, increase in PH and TRV was similar in both treatments. The mean annual T was similar between treatments (15.0 L m-2 month-1). The highest T was recorded in October/2014 (IT = 33.0 L m-2 month-1) and July/2015 (NIT = 20.5 L m-2 month-1). The greater LA and water deficit blades DEF > 30 mm promoted lower transpiration in the irrigated plants. Irrigation maintained plant growth in PH, DBH, and LA in the third year, even after irrigation has ceased. However, non-irrigated plants were similar in TRV (0.065 m3) and transpiration rates (≈ 15 L m-2 month-1). Winter transpiration (11.3 L m-2 month-1) was lower than in summer (18.8 L m-2 month-1) for irrigated plants and similar for non-irrigated plants (≈ 14 L m-2 month-1). Based on that, in order to maintain the homogeneity of the plants, the irrigation in the first 2 years of cultivation is recommended, and also, the sap flow measures presented satisfactory results regarding the determinations of the water needs of African mahogany.