Combination of Callyspongia sp. and Stem Cells for Wound Repair and Skin Regeneration: in Vivo and in Silico Evidences.

Delayed healing of chronic wounds results in amputation and mortality rates in serious cases. The present study examines the merged wound-restorative efficacy of injectable bone marrow-derived mesenchymal stem cells (BMMSCs) and topical Callyspongia sp. extract in immunocompromised rats. HR-LC-MS analysis of Callyspongia sp. extract tentatively identified twenty-nine compounds (1-29) and highlighted its richness in fatty acids and terpenoids, known for their wound regenerating efficacies. The wound closure was greatly prominent in the BMMSCs/Callyspongia sp. group in contrast to the control group (p<0.001). The RT-PCR gene expression emphasized these results by attenuating the oxidative, inflammatory, and immunity markers, further confirmed by histopathological findings. Additionally, in silico modeling was particularly targeting matrix metalloproteinase-9 (MMP9), a key player in wound healing processes. Computational analysis revealed that compounds 18 and 19 potentially modulate MMP9 activity. The combination of BMMSCs and topical Callyspongia sp. extract holds a promise for regenerative therapy constituting a drastic advance in the wound cure of immunocompromised patients, eventually further safety assessments and clinical trials are required.

Tamarix aphylla derived metabolites ameliorate indomethacin-induced gastric ulcers in rats by modulating the MAPK signaling pathway, alleviating oxidative stress and inflammation: In vivo study supported by pharmacological network analysis.

Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1ß, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.

Anti-otomycotic potential of nanoparticles of Moringa oleifera leaf extract: an integrated in vitro, in silico and phase 0 clinical study.

Otomycosis is a serious superficial mycotic infection of the outer ear canal caused by some pathogenic species of Candida and Aspergillus. The infection remains a challenge to clinicians owing to the incomplete efficacy of market-available antifungal agents and high recurrence rates. The Moringa oleifera leaf ethanol extract showed efficacy against Candida albicans SC5314, compared to Nystatin® as a reference with MIC values of 7 and 718.33 µg ml-1, respectively. The extract was mixed with lecithin and chitosan to give Moringa core/shell giant nanoparticles, with a good zeta potential (+59.2 mV), a suitable entrapment efficiency (61%) and an enhanced release reaching up to 90% at 8 h. Clinical isolates from oomycote patients were identified via DNA sequencing as Candida parapsilosis, Aspergillus niger and Aspergillus flavus, and the effect of the prepared nanoparticles was tested against them via disk diffusion assay to give inhibition zones of 75, 55 and 55 mm, compared to Nystatin® with 35, 25 and 20 mm, respectively. Interestingly, patients treated with the Moringa-loaded nanoparticles experienced improvement within 1 week with no recurrence for more than 3 months. To have some insight into the bioactive components in the Moringa extract, LC-HRMS-based identification has been employed which led to the annotation of 27 compounds. Subsequent comprehensive in silico investigation suggested some alkaloids to be responsible for the activity targeting the fungal 14-α-demethylase enzyme (CYP51B). Our study revealed that Moringa extract-loaded nanoparticles attained an enhanced antifungal efficacy compared to Nystatin® and therefore they can be employed against invasive and drug-resistant otomycotic infections.

Metabolomic Profiling and Cytotoxic Tetrahydrofurofuran Lignans Investigations from Premna odorata Blanco.

Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC-HRESIMS. The identified metabolites (1-34) belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4ß-hydroxyasarinin 35, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds 35-38 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound 35 had cytotoxic effects against HL-60 and MCF-7 with IC50 values of 2.7 and 4.2 µg/mL, respectively. A pharmacophore map of compounds 35 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature aligning the central hydroxyl group and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target's active site.

New Antiproliferative Cembrane Diterpenes from the Red Sea Sarcophyton Species.

The combination of liquid chromatography coupled to high resolution mass spectrometry (LC-HRESMS)-based dereplication and antiproliferative activity-guided fractionation was applied on the Red Sea-derived soft coral Sarcophyton sp. This approach facilitated the isolation of five new cembrane-type diterpenoids (1-5), along with two known analogs (6 and 7), as well as the identification of 19 further, known compounds. The chemical structures of the new compounds were elucidated while using comprehensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional (2D) NMR and HRMS. All of the isolated cembranoids (1-7) showed moderate in vitro antiproliferative activity against a human breast cancer cell line (MCF-7), with IC50 ranging from 22.39-27.12 µg/mL. This class of compounds could thus serve as scaffold for the future design of anticancer leads.