Metabolomic study of the estrogenic and anti-osteoporotic potential of Erythrina bidwillii leaf.

Erythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and gas chromatography-mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8-oxoerythraline (2), (+)-erythrinine (3), (+)-erythraline (4) and 8-oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti-osteoporotic, anti-hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF-7 cell lines. An in silico study of the isolated metabolites revealed that (+)-erythrinine (3) and 8-oxoerythrinine (5) exhibited the highest affinity for ERα and ERß, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials.

HPLC and GC-MS-based metabolic profiles and in vivo anticonvulsant, sedative, and antinociceptive potentials of truffles Tirmania nivea and Tirmania pinoyi hydromethanolic extracts in mice.

GC-MS and HPLC analyses of the hydromethanolic extracts of the truffles Tirmania nivea (TN) and Tirmania pinoyi (TP) revealed the presence of 18 metabolites and 11 polyphenols, respectively. In vivo, TP extract protected against subcutaneous pentylenetetrazole (scPTZ) and maximal electric shock (MES)-induced convulsions faster than TN extract. TP extract (100 and 300 mg/kg) showed 100% protection and longer duration than TN extract in the scPTZ test. Similarly, at 300 mg/kg, TP demonstrated a quicker start (75%) and longer duration of action (100%) than TN in MES test. In the scPTZ test, ED50 of TP demonstrated greater anticonvulsant efficacy than that of TN. In mice given TP and TN treatments, the brain GABA levels noticeably increased. TP (100 and 300 mg/kg) produced a notable sedative effect in open-field test, whereas TN (100 or 300 mg/kg) and TP (300 mg/kg) reduced sleep latency by 52%, 45%, and 79%, respectively. In writhing test, TN (100 or 300 mg/kg) significantly enhanced analgesic efficacy by 50 and 87%, respectively. Comparatively, in formalin test, TP and TN at a dosage of 300 mg/kg decreased the length of the licking by 34 and 59%, respectively. For the first time, this study explains the anticonvulsant, sedative, central, and peripheral analgesic activities of truffle extracts.

In vitro wound healing properties, antioxidant activities, HPLC-ESI-MS/MS profile and phytoconstituents of the stem aqueous methanolic extract of Dracaena reflexa Lam.

Column chromatography of the stem aqueous methanolic extract of Dracaena reflexa Lam. (DRSE) led to the isolation of five flavonoids, one phenolic glycoside, one triterpenoid and two steroidal saponins. Furthermore, 44 compounds were tentatively identified in the phytoconstituent profile of DRSE using HPLC-ESI-MS/MS. The antioxidant activity of DRSE was evaluated. In a DPPH radical scavenging assay, DRSE exhibited an IC50 value of 311.6 ± 10.10 µg/ml compared with the IC50 value of the standard Trolox (24.42 ± 0.87 µg/ml). The antioxidant activities of DRSE using ABTS assay and ferric reducing antioxidant power assay were 326.63 µm Trolox equivalents/mg extract and 208.67 µm Trolox equivalents/mg extract, respectively. The wound-healing activity of DRSE was studied by the scratch assay using Human Skin Fibroblast cells. After 24 h DRSE (at 10 and 20 µg/ml) decreased the wound width to 0.55 ± 0.37 and 0.47 ± 0.55 mm, respectively, compared with the wound width in the control cells (0.77 ± 0.17 mm). This result suggested that DRSE improved the wound-healing process by inducing the migration of fibroblasts. Moreover, a docking study was performed to evaluate the binding affinity of the identified phytoconstituents toward GSK-3ß relative to the co-crystalized inhibitor and curcumin with the possible involvement of this pathway in the wound-healing activity of the extract.

Antiproliferative potential of moluccella laevis L. aerial parts family lamiaceae (labiatae), supported by phytochemical investigation and molecular docking study.

The current biologically guided study aimed the in vitro investigation of cytotoxic activity, identification of the phytochemical content of Moluccella laevis L. aerial parts and supporting this activity by a molecular docking study. Aqueous fraction demonstrated the most potent cytotoxic effect against CACO-2 with IC50 = 0.067 ± 0.01 µg/mL. Furthermore, EtOAc fraction showed a remarkable cytotoxic activity against MCF-7 cell line with IC50 = 0.35 ± 0.02 µg/mL. Consequently, total ethanolic extract (TEE) and its fractions were subjected to LC-HR-ESI-MS metabolic profiling to discover the constituents that possibly underlie their cytotoxicity. Twenty compounds were tentatively identified from metabolic analysis. Furthermore, eight compounds were isolated. In silico docking study revealed that stachydrine is more likely to account for the antiproliferative activity of both EtOAc and aqueous fractions, probably via its moderate inhibition of receptor tyrosine kinases. [Formula: see text].

NS3/4A helicase inhibitory alkaloids from Aptenia cordifolia as HCV target.

Chemical investigation of Aptenia cordifolia roots extract, using chromatographic and spectroscopic techniques, resulted in isolation and identification of eight known compounds. The basic ethyl acetate fraction (alkaloidal fraction) afforded O-methylsceletenone, epinine, 4-methoxy phenethylamine, and N-methyl tyramine while, the acidic ethyl acetate fraction (non-alkaloidal fraction) afforded only cis-N-coumaroyl tyramine. Moreover, the petroleum ether fraction afforded capric acid, tricosanol, and a mixture of ß-sitosterol & stigma sterol. Upon screening of anti HCV activity of these three fractions, only the basic ethyl acetate fraction had high activity against HCV with an IC50 value equal to 2.4 µg mL-1 which provoked us to carry out structure based in silico virtual screening on the drug targets of HCV of isolated alkaloidal compounds as well as the previously dereplicated alkaloids through metabolomics from the antiviral active fraction. The tortuosamine compound exhibited the strongest binding to the active site of NS3/4A helicase with a binding affinity (-7.1 kcal mol-1) which is very close to the native ligand (-7.7 kcal mol-1).

Neuroprotective activity of Ulmus pumila L. in Alzheimer's disease in rats; role of neurotrophic factors.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders which affects the hippocampus and cortical neurons leading to impairment of cognitive ability. Treatment of AD depends mainly on acetylcholinesterase inhibitors, however, a novel therapeutic approach is introduced based on the maintenance of neuronal viability and functionality exerted through neurotrophic factors. In the current study, Ulmus pumila L. leaves alcoholic extract was investigated for its neuroprotective activity in AlCl3-induced AD in rats. Rats were orally treated with AlCl3 (17 mg/kg) for 4 weeks followed by U. pumila extract (150 mg/kg b.wt.) for another 6 weeks. Treatment of neuro-intoxicated rats with U. pumila extract resulted in a significant regulation in neurotrophic factors; brain derived neurotrophic factor and transforming growth factor-ß and pro-inflammatory cytokine; TNF. It also induced an elevation in serum levels of monoamine neurotransmitters; norepinephrine, dopamine and serotonin and a decline in brain acetlycholinesterase activity. U. pumila extract also showed potent antioxidant activity as indicated by the declined malondialdehyde and elevated reduced glutathione, catalase and super oxide dismutase levels in AD rats' brains. Histological improvement was detected in the cerebral cortex, the hippocampus and striatum of the treated rats. The phytochemical analysis of U. pumila extract revealed high contents of flavonoids and phenolics and the major compounds were isolated and chemically characterized. Additionally, U. pumila extract and the isolated compounds exerted a prominent activity in in-vitro acetylcholinesterase inhibition assay with kaempferol-3-O-ß-glucoside being the most potent compound showing IC50 of 29.03 ± 0.0155 µM. A molecular docking study indicated high affinity of kaempferol-3-O-ß-robinobioside on acetylcholine esterase binding site with estimated binding free energy of -8.26 kcal/mol.

Sulawesins A-C, Furanosesterterpene Tetronic Acids That Inhibit USP7, from a Psammocinia sp. Marine Sponge.

Three new furanosesterterpene tetronic acids, sulawesins A-C (1-3), were isolated from a Psammocinia sp. marine sponge, along with the known compounds ircinins-1 (4) and -2 (5). Although ircinins-1 and -2 were previously isolated as (+)- or (-)-enantiomers from marine sponges, we isolated them as enantiomeric mixtures. Sulawesins A and B possess a new carbon skeleton with a 5-(furan-3-yl)-4-hydroxycyclopent-2-enone moiety and were also found to be diastereomeric mixtures of four isomers by an HPLC analysis with a chiral-phase column. Sulawesin C has a dimeric structure of ircinin-1 and is the first dimer in this family. USP7, a deubiquitinating enzyme, is an emergent target of cancer therapy, and the isolated compounds inhibited USP7 with IC50 values in the range of 2.7-4.6 µM.

MRI in perianal fistulae.

MRI has become the method of choice for evaluating perianal fistulae due to its ability to display the anatomy of the sphincter muscles orthogonally, with good contrast resolution. In this article we give an outline of the classification of perianal fistulae and present a pictorial assay of sphincter anatomy and the MRI findings in perianal fistulae. This study is based on a retrospective analysis of 43 patients with a clinical diagnosis of perianal fistula. MRI revealed a total of 44 fistulae in 35 patients; eight patients had only perianal sinuses.