Lantana camara leaf extract ameliorates memory deficit and the neuroinflammation associated with scopolamine-induced Alzheimer's-like cognitive impairment in zebrafish and mice.

CONTEXT: Lantana camara Linn. (Verbenaceae) is used for improving memory in certain African societies. OBJECTIVE: This study investigated the effect of prophylactic treatment with hydroethanolic leaf extract of Lantana camara (LCE) on short-term memory deficit and neuroinflammation induced with scopolamine in zebrafish and mice. MATERIALS AND METHODS: Zebrafish (AB strain) and mice (ICR) were given donepezil (0.65 mg/kg, oral) and LCE (10, 30, 100 mg/kg, oral) for 7, and 10 days, respectively, before induction of cognitive impairment with scopolamine immersion (200 µM) and intraperitoneal injection (2 mg/kg), respectively. Spatial short-term memory was assessed in zebrafish using both Y- and T-mazes, whereas Y-maze was used in mice. Mice hippocampal and cortical tissues were analyzed for mRNA expression of proinflammatory genes (IL-1ß, IL-6, TNF-α, COX-2) using qRT-PCR. RESULTS: In the zebrafish Y-maze, LCE (10 and 100 mg/kg) increased time spent in the novel arm by 55.89 ± 5.70%, and 68.21 ± 2.75%, respectively, but not at 30 mg/kg. In the zebrafish T-maze, there was an increase in time spent in the food-containing arm at 30 (44.23 ± 2.13) and 100 mg/kg (52.30 ± 1.94). In the mouse Y-maze, spontaneous alternation increased by 52.89 ± 4.98% at only 10 mg/kg. LCE (10, 30, 100 mg/kg) inhibited proinflammatory gene (IL-1ß, IL-6, TNF-α, COX-2) mRNA expression, with the highest inhibitory effect on IL-6 in both the hippocampus (83.27 ± 2.49%; 100 mg/kg) and the cortex (98.74 ± 0.11%; 10 mg/kg). DISCUSSION AND CONCLUSION: LCE ameliorated scopolamine-induced AD in both zebrafish and mice.

Evaluation of the anti-inflammatory and antioxidant potential of the stem bark extract and some constituents of Aidia genipiflora (DC.) dandy (rubiaceae).

Aidia genipiflora (DC.) Dandy (Rubiaceae) is used to treat various microbial and inflammatory conditions by traditional healers in West African countries. However, there is no information on anti-inflammatory potential of A. genipiflora. This work therefore provides information on the anti-inflammatory and the antioxidant activities of the stem bark extracts and some bioactive constituents of Aidia genipiflora. Method: The anti-inflammatory activities of the extracts and compounds from A. genipiflora were investigated using the carrageenan-induced footpad oedema assay and the egg albumin denaturation assay. The antioxidant activities of the extract and compounds were investigated using the DPPH radical scavenging assay and the phosphomolybdenum total antioxidant capacity assay. The whole extract of A. genipiflora was also investigated for its acute oral toxicity using the fixed-dose procedure described by the Organization for Economic Cooperation Development guidelines. Result: The whole extract showed no acute toxicity effect and the LD50 was estimated to be greater than 3000 mg/kg body weight. The whole extract, methanol, and ethyl acetate fractions (30, 100, and 300 mg/kg) showed in vivo anti-inflammatory activity with respective percentage inhibition of oedema of 45.11 ± 3.41, 31.12 ± 3.42 and 29.28 ± 3.58 (p < 0.001) at the highest dose of 300 mg/kg. Diclofenac, used as a reference drug, gave a % inhibition of 48.94 ± 3.58. The compounds isolated from A. genipiflora demonstrated in-vitro anti-inflammatory activity at the IC50 range (16-96 µg/mL) compared to diclofenac (IC50 of 74.48 µg/mL). Oleanonic acid (AG1) and D-mannitol (AG4) further demonstrated in vivo anti-inflammatory activity (ED50 = 20.61 ± 1.29; 23.51 ± 1.26 mg/kg respectively) which was less potent compared to diclofenac (ED50 = 12.50 ± 1.41 mg/kg) in the carrageenan-induced oedema assay. The whole extract, pet. ether, ethyl acetate, and methanol fractions of A. genipiflora exhibited DPPH scavenging activities with respective IC50 of 222.2, 169.7, 121.5, and 40.7 µg/mL. The whole extract of A. genipiflora exhibited considerable total antioxidant capacity with respective values of 248.5 mg/g of ascorbic acid equivalent. All the compounds exhibited low DPPH scavenging activity with IC50 (64-86 µg/mL), compared to ascorbic acid (IC50 of 3.13 ± 1.20 µg/mL). These results highlight the anti-inflammatory and antioxidant activities of Aidia genipiflora stem bark extract and its constituents as evidence to support its traditional uses.

Antinociceptive effects of a hydroethanolic stem bark extract of Burkea africana.

INTRODUCTION: Pain is a major symptom of many clinical disorders and its relief has long been a concern for individuals across the globe. There is therefore an unmet need to search for new efficacious agents for the effective management of pain. The stem bark of the savanna tree Burkea africana (Hook) (Family: Leguminosae) is used in the Ghanaian traditional medicine for the treatment and management of various pain-related diseases. METHOD: An acute oral toxicity study in mice was conducted by administering BAE (50-5000 mg kg-1 p.o.). Antinociceptive effect of BAE (50-1000 mg kg-1 p.o.) was evaluated using the acetic acid-induced abdominal constriction, acidic saline-induced muscle pain and formalin-induced pain models. The antinociceptive mechanism of BAE was also assessed using the formalin-induced pain model. RESULTS: The LD50 of BAE was thus estimated to be above 5000 mg kg-1 since none of the animals died in the acute toxicity study. Pretreatment with BAE (50-1000 mg kg-1 p.o.) significantly reduced the number of writhes after acetic-acid administration compared to the vehicle treated group. BAE also produced a significant and dose-dependent reversal of mechanical hyperalgesia induced by the injection of the acidic saline. Administration of BAE was able to significantly suppress both phases of the formalin test. This effect of the extract was however reversed by pretreatment with naloxone and granisetron. CONCLUSIONS: BAE exhibits antinociceptive effects in rodent pain models with a possible involvement of 5-HT3 receptors and opioidergic pathways.

Amphimas pterocarpoides harms.: An Evaluation of flavonoid and phenolic contents, wound healing, anthelmintic and antioxidant activities of the leaves and stem bark.

The present study evaluated the wound healing, anthelmintic and antioxidant potentials of crude methanol extracts and fractions (petroleum ether, ethyl acetate and methanol) of the leaves and stem bark of Amphimas pterocarpoides. Wound healing activity was determined by the dermal excision model in rats; anthelmintic activity was evaluated by the adult worm motility test using the adult Indian worm, Pheretima postuma. Total flavonoid, phenolic content and antioxidant activity were assessed by the aluminum chloride colorimetric, Folin Ciocalteu, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and total antioxidant capacity (TAC) assays respectively. HPLC/UV fingerprints were developed for quality control. The maximum amount of phenolics and flavonoids were detected in the methanol fractions of the stem bark (225.0 ± 20.0 mg/g gallic acid equivalent (GAE) and 201.0 ± 1.41 mg/g quercetin equivalent (QCE) respectively) and leaves (84.54 ± 1.36 mg/g GAE and 130.7 ± 1.71 mg/g QCE, respectively). Both leaf and bark displayed remarkable free radical scavenging and TAC with the highest effect given by the methanol fractions. Significant (p < 0.05) wound contraction was achieved by topical application of the leaf (APL) and stem bark (APS) ointments (5-15%) with >90 % wound surface closure for 1% silver sulphadiazine, APS 15% and APL 10% treated groups by day 15. APL and APS demonstrated a concentration- and time-dependent paralysis and mortality of the P. posthuma with APL (6.25 mg/mL) causing worm paralysis at 82.60 min and death at 93 min, better than 10 mg/mL albendazole (paralysis at 76.30 min; death at 117 min). Tannins, triterpenoids, phytosterols, flavonoids, saponins and coumarins were detected in the leaves and bark. The results have proven the potential of A. pterocarpoides as a wound healing and anthelmintic agent, giving scientific credence to its use in traditional medicine.

The Effectiveness of Varying Combination Ratios of A. cordifolia and M. indica against Field and Laboratory Strains of P. falciparum In Vitro.

BACKGROUND: Drug resistance in malaria is a global problem, with reports of Plasmodium parasites resistant to the current first-line antimalarial drug, artemisinin, expanding from Southeast Asia to Africa. There is therefore an urgent need to identify new drug candidates that will be effective against the existing malaria parasites. Drug combination therapy presents a myriad of advantages over monotherapy including delayed onset of resistance, potentiation, and synergism. This present study explored the effectiveness of combinations of aqueous extracts of Alchornea cordifolia (A. cordifolia) and Mangifera indica (M. indica) at clearing both laboratory and field isolates of P. falciparum. METHODS: Synchronized ring stage cultures of field (FA08) and laboratory strains (NF54 and CamWT_C580Y) of P. falciparum were subjected to combinations of different concentrations and ratios of aqueous extracts of A. cordifolia and M. indica. The growth inhibition of the individual plant extracts and their combinatory effects were studied in vitro using SYBR Green I drug assay. RESULTS: The A. cordifolia extract exhibited 50% inhibitory concentration (IC50) of 2.71, 7.80, and 3.56 µg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Mangifera indica exhibited IC50 of 18.11, 20.08, and 10.23 µg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Additive, synergistic and antagonistic interactions were observed at different combinations of A. cordifolia and M. indica extracts. CONCLUSION: A combination product containing A. cordifolia and M. indica has the potential to serve as an effective antimalarial as majority of the tested combinations of aqueous extracts of A. cordifolia and M. indica extracts exhibited synergistic effects in vitro against the NF54, CamWT_C580Y, and FA08 P. falciparum strains.

Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats.

Context. The stem bark of the savanna tree Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. OBJECTIVE: This study seeks to investigate the possible antiallodynic and antihyperalgesic effects of the hydroethanolic stem bark extract of B. africana in a vincristine-induced peripheral neuropathy model in rats. Materials and Methods. 0.1 mg kg-1 vincristine was administered intraperitoneally for 5 days followed by 2 days break and continued for another 5 days to establish peripheral neuropathy in Sprague Dawley rats. Effects of Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. p.o.) and pregabalin (10-100 mg kg-1, i.p.) were assessed on tactile, intermediate, mechanical, cold, and hot allodynia as well as in the Randall-Sellito test. Moreover, the levels of total proteins, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in sciatic nerve tissue homogenates were assayed. RESULTS: BAE (50-1000 mg kg-1 p.o.) showed significant antiallodynic and antihyperalgesic effects similar to pregabalin by increasing paw withdrawal latency and paw withdrawal threshold in all the behavioral tests used. Also, the extract decreased the levels of MDA (a lipid peroxidation product) as well as MPO and caused a significant increase in endogenous antioxidants (GSH) and antioxidant enzymes (SOD and CAT) in tissue homogenates of treated rats. CONCLUSIONS: Results from this study indicate that the hydroethanolic stem bark extract of B. africana exhibits antiallodynic and antihyperalgesic effects in vincristine-induced peripheral neuropathy in rats.B. africana in a vincristine-induced peripheral neuropathy model in rats.

Hypotensive and Antihypertensive Properties and Safety for Use of Annona muricata and Persea americana and Their Combination Products.

INTRODUCTION: In the management of hypertension (a cardiovascular disease and the leading metabolic risk factor in noncommunicable diseases) with herbal medicines, efficacy and safety are of uttermost concern. This study sought to establish hypotensive, antihypertensive, drug interaction, and safety for use of the aqueous leaf extracts of Annona muricata (AME), Persea americana (PAE), or their combination products (CAPE). Methodology. Systolic and diastolic blood pressure (SBP and DBP), mean arterial blood pressure (MAP), and heart rate (HR) were measured in normotensive Sprague-Dawley rats treated with 50-150 mg/kg of AME, PAE, or CAPE to establish a hypotensive effect. "Combination index" was calculated to establish interaction between AME and PAE. The antihypertensive effect of CAPE was established by measuring SBP, DBP, MAP, and HR in ethanol-sucrose- and epinephrine-induced hypertension. Full blood count, liver and kidney function tests, and urinalysis were determined in ethanol/sucrose-induced hypertension to establish safety for use. RESULTS: AME, PAE, and CAPE significantly (p ≤ 0.001) decreased BP in both normotensive and hypertensive animals. Effects of CAPE 1, CAPE 2, and CAPE 3 were synergistic (combination indices of 0.65 ± 0.07, 0.76 ± 0.09, and 0.87 ± 0.07, respectively). There was a significant decrease (p ≤ 0.01 - 0.001) in SBP and MAP with 100 mg/kg CAPE 1 and 75 mg/kg CAPE 2 treatment in hypertension as well as with nifedipine (p ≤ 0.001) treatment. Epinephrine-induced hypertension in anesthetized cats was significantly and dose-dependently inhibited (p < 0.05 - 0.001) by 25-100 mg/ml CAPE 1 and 37.5-75 mg/ml CAPE 2. CAPE administration had no deleterious effect (p > 0.05) on full blood count, liver and kidney function, and urine composition in hypertensive rats. CONCLUSION: The aqueous leaf extracts of Annona muricata, Persea americana, and their combination products possess antihypertensive properties, with combination products showing synergism and safety with use.

Resistance Modulation Action, Time-Kill Kinetics Assay, and Inhibition of Biofilm Formation Effects of Plumbagin from Plumbago zeylanica Linn.

Antimicrobial resistance (AMR) is a threat to the prevention and treatment of the increasing range of infectious diseases. There is therefore the need for renewed efforts into antimicrobial discovery and development to combat the menace. The antimicrobial activity of plumbagin isolated from roots of Plumbago zeylanica against selected organisms was evaluated for resistance modulation antimicrobial assay, time-kill kinetics assay, and inhibition of biofilm formation. The minimum inhibitory concentrations (MICs) of plumbagin and standard drugs were determined via the broth microdilution method to be 0.5 to 8 µg/mL and 0.25-128 µg/mL, respectively. In the resistance modulation study, MICs of the standard drugs were redetermined in the presence of subinhibitory concentration of plumbagin (4 µg/mL), and plumbagin was found to either potentiate or reduce the activities of these standard drugs with the highest potentiation recorded up to 12-folds for ketoconazole against Candida albicans. Plumbagin was found to be bacteriostatic and fungistatic from the time-kill kinetics study. Plumbagin demonstrated strong inhibition of biofilm formation activity at concentrations of 128, 64, and 32 µg/mL against the test microorganisms compared with ciprofloxacin. Plumbagin has been proved through this study to be a suitable lead compound in antimicrobial resistance drug development.