A novel nor-megastigmane from the leaves of Rhaphiostylis beninensis.

A novel nor-megastigmane, normegastigmane-5α,9-epoxy-3ß,8-diol (1), together with 10 known compounds of diverse classes including megastigmanes, sesquiterpenoids, and triterpenoids were isolated from the leaves of Rhaphiostylis beninensis. The structure of 1 was established by 1D and 2D NMR and HRESIMS data analysis. The known compounds were identified as 5,11-epoxy-3,9-megastigmanediol (2), 7-megastigmene-3,6,9-triol (3), 1,3-dihydroxypropan-2-yl stearate (4), (1E,5E)-1,5-dimethyl-8-(propan-2-ylidene)cyclodeca-1,5-diene germacrene (5) 3,5-dihyroxy-6,7-megastigmadien-9-one (6), squalene (7), ß-amyrin (8), ß-amyrone (9), ß-amyrin eicosanoate (10), and ß-sitosterol (11). Compounds 2, 3, and 6 displayed inhibitory effects on acetylcholinesterase enzyme. This is the first report of these compounds from the plant and their anticholinesterase activity.

Protein Tyrosine Phosphatase 1B Inhibitory Iridoids from Psydrax subcordata.

Phytochemical investigation of the leaves and bark of Psydrax subcordata has led to the isolation of six new iridoids, subcordatanols I-V (1-4 and 6) and 1-O-methylcrescentin I (5), along with two known analogues (7 and 8). Among them, subcordatanol I (1) is the first example of a 3,8-monoepoxy-iridoid featuring a caged 2-oxa-bicyclo[3.2.1]octane core. The absolute stereochemistry at C-4 of 3, 4, and 6 was established through their acid-catalyzed reaction products subcordatalactones A (3a), B (4a), and C (6a), respectively. Subcordatanols I (1) and II (2), as well as subcordatalactones A (3a) and B (4a), displayed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Enzyme kinetic studies indicated that 3a and 4a are competitive inhibitors. A molecular docking study is also reported.

Antifungal and antiproliferative activities of endophytic fungi isolated from the leaves of Markhamia tomentosa.

CONTEXT: Plants harbor endophytes with potential bioactivity. Markhamia tomentosa (Benth) K. Schum ex. Engl. (Bignoniaceae) is reported to possess antioxidant, anti-inflammatory and anticancer activities. OBJECTIVE: The antifungal and antiproliferative properties of endophytic fungi extracts and fractions from M. tomentosa were evaluated. MATERIAL AND METHODS: Endophytic fungi were isolated from the leaves of M. tomentosa and identified by ITS-rDNA sequence analysis. The antagonistic effect of the fungal strains was investigated against pathogenic fungi viz, Fusarium oxysporum, Sclerotinia sclerotiorium, Rhizoctonia solani, and Botrytis cinerea using the dual culture assay for 5-7 days. Antiproliferative effect of the fungal extracts and fractions (3.91-250 µg/mL) on HeLa cancer cell line was tested and IC50 was calculated. Poisoning food assay and antifeedant activity against the pathogenic fungi and Spodoptera litura larvae, for 7 days and 2 h, respectively, was also tested at concentrations of 250, 500 and 1000 µg/mL. RESULTS: Fungal endophytes Trichoderma longibrachiatum and Syncephalastrum racemosum were isolated from the leaves of M. tomentosa. Isolated endophytic fungal strains and solvent extracts showed MIC value of 1000 µg/mL against tested pathogenic fungi in the dual culture and poisoning food assays. Methanol fraction of S. racemosum isolate showed the most effective antiproliferative activity with IC50 of 43.56 µg/mL. Minimal feeding deterrent activity against S. litura larvae was also observed. DISCUSSION AND CONCLUSION: These findings showed that the leaves of Markhamia tomentosa harbor strains of endophytic fungi with promising health benefits, and suggest their antifungal and antiproliferative effects against pathogenic fungi and HeLa cancer cell line.

Sub-acute and chronic toxicity profiles of Markhamia tomentosa ethanolic leaf extract in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Markhamia tomentosa (Benth.) K. Schum Ex Engl. (Bignoniaceae) is used in traditional African medicine for the treatment of diarrhoea, oedema, pain and malaria. The leaf extract was reported to show no visible sign of toxicity on acute exposure. This present study investigates the sub-acute and chronic toxicity effects of Markhamia tomentosa in rats. MATERIALS AND METHODS: The animals (n=6/group) were treated daily with the extract at doses of 40, 200 and 1000mg/kg orally for 28 and 90 days. Control rats received distilled water and all animals were weighed at 7 days interval. The haematological, biochemical and histological parameters were determined. RESULTS: The extract showed non-significant changes in body weight gain of treated compared to control rats in both studies. Extract significantly decreased red blood cell (RBC), mean cell haemoglobin concentration and increased mean corpuscular volume (MCV) parameters after the 28 day study. In the 90 day study, a significant increase in white blood cell, RBC, platelets and decrease in MCV and mean cell haemoglobin (MCH) parameters were observed. Biochemical parameters were significantly changed in both studies; triglycerides, total protein, alanine transaminase, aspartate transaminase and albumin showed significant increase while creatinine, blood urea nitrogen and uric acid levels showed significant decrease. Significant increase in liver weight with no treatment-related histological changes was observed in all harvested vital organs. CONCLUSION: Markhamia tomentosa extract elicited non-toxic effect in the liver and kidney function parameters in rats. Thus, the extract is safe when administered orally.

Review of the Phytochemical and Pharmacological Studies of the Genus Markhamia.

Natural product compounds obtained from medicinal plants have been great contributions in the discovery of numerous clinically useful drugs. Markhamia species have been reportedly used by many cultures in human and veterinary traditional medicines. The five identified species of Markhamia, that is, Markhamia lutea, Markhamia obtusifolia, Markhamia stipulata, Markhamia tomentosa, and Markhamia zanzibarica have been the subject of chemical investigations that have led to the characterization of their secondary metabolites. Plants of the genus with the identified phytoconstituents, including phenylpropanoid glycosides (PhGs), terpenoids, phytosterols, lignans, quinones, and flavonoids, have been claimed to possess antiviral, antifungal, antiprotozoal, analgesic, antiinflammatory, and cytotoxic activities. In vitro and in vivo pharmacological research studies have reported the validation of the medicinal properties of plants of this genus. The present review analyzes published data from the ethnomedicinal, phytochemical, and pharmacological studies of plants of the genus Markhamia.

Antiproliferative and apoptosis inducing activity of Markhamia tomentosa leaf extract on HeLa cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Markhamia tomentosa (Benth) K. Schum ex. Engl. (Bignoniaceae), a tree widely dispersed in West Tropical Africa, is used traditionally to treat various diseases as it possesses antimicrobial, antioxidant, analgesic, anticancer and anti-inflammatory activities. MATERIALS AND METHODS: This study evaluates the cytotoxic effect and underlying mechanisms of the ethanolic extract of Markhamia tomentosa on HeLa and MCF-7 cancer cell lines and non-cancerous Vero cell line. Brine shrimp lethality test was used for preliminary screening. Cytotoxicity was determined using the MTT assay and IC50 was calculated. Effect of Markhamia tomentosa on the cell cycle was monitored by flow cytometry and the apoptosis-induction capability confirmed by exposure of phosphatidylserine to the outer leaflet of the plasma membrane. Loss of mitochondrial membrane potential was analysed by flow cytometry using JC-1. RESULTS: Markhamia tomentosa was toxic to brine shrimps with LD50 of 31.62µg/ml. Cell viability and growth of HeLa cells was inhibited by the extract with an IC50 of 189.1±1.76µg/ml at 24h post treatment. However, no cytotoxic effect was observed in MCF-7 and Vero cell lines. The extract induced cell cycle arrest in HeLa cells in the G0/G1 phase resulting in cell death after 24h exposure. Induction of apoptosis in HeLa cells was substantiated by Annexin V-FITC/PI double staining showing phosphatidylserine translocation and depolarisation of the mitochondrial membrane potential by flow cytometry of JC-1 stained cells. CONCLUSION: The ethanolic extract of Markhamia tomentosa induces G0/G1 in HeLa cells followed by induction of the intrinsic pathway of apoptosis.

Phenolic contents, antioxidant and antibacterial activities of Hymenocardia acida.

This study investigates the antioxidant and antibacterial activities of aqueous and methanolic extracts from Hymenocardia acida Tul. (Hymenocardiaceae). The inhibition values of the extracts and quercetin were found to be very close, with no significant differences at a concentration of 0.05 mg mL(-1) in their ability to inhibit 1,1-diphenyl-2-picrylhydrazyl (DPPH). Total proanthocyanidins for both water and methanol extracts were 20.2 +/- 0.01 and 30.6 +/- 0.51 mg g(-1) (catechin equivalent) while the total phenol contents were 20.0 +/- 0.52 and 35.6 +/- 1.42 mg mL(-1) (tannic acid equivalent), respectively. Positive correlations R(2) = 0.85, R(2) = 0.94, R(2) = 0.97 for DPPH, reducing power and 2'-azino-bis(3-ethylbenzo thiazoline)6-sulphonic acid (ABTS). Linear regression analysis also produced a high correlation coefficient with total proanthocyanidins (DPPH, R(2) = 0.69; ABTS, R(2) = 0.94). H. acida extracts showed low antibacterial activity (minimum inhibitory concentration (MIC) value >or=5.0 mg mL(-1)) against gram negative bacteria but significantly (MIC value