Moringa oleifera Lam. (Moringaceae) is an adaptable plant with promising phytoconstituents, interesting medicinal uses, and nutritional importance. Chemical profiling of M. oleifera seeds assisted by LC-HRMS (HPLC system coupled to a high resolution mass detector) led to the dereplication of 19 metabolites. Additionally, the wound healing potential of M. oleifera seed extract was investigated in male New Zealand Dutch strain albino rabbits and supported by histopathological examinations. Moreover, the molecular mechanisms were investigated via different in vitro investigations and through analyzing the relative gene and protein expression patterns. When compared to the untreated and MEBO^®-treated groups, topical administration of M. oleifera extract on excision wounds resulted in a substantial increase in wound healing rate (p < 0.001), elevating TGF-β1, VEGF, Type I collagen relative expression, and reducing inflammatory markers such as IL-1β and TNF-α. In vitro antioxidant assays showed that the extract displayed strong scavenging effects to peroxides and superoxide free radicals. In silico studies using a molecular docking approach against TNF-α, TGFBR1, and IL-1β showed that some metabolites in M. oleifera seed extract can bind to the active sites of three wound-healing related proteins. Protein–protein interaction (PPI) and compound–protein interaction (CPI) networks were constructed as well. Quercetin, caffeic acid, and kaempferol showed the highest connectivity with the putative proteins. In silico drug likeness studies revealed that almost all compounds comply with both Lipinski’s and Veber’s rule. According to the previous findings, an in vitro study was carried out on the pure compounds, including quercetin, kaempferol, and caffeic acid (identified from M. oleifera) to validate the proposed approach and to verify their potential effectiveness. Their inhibitory potential was evaluated against the pro-inflammatory cytokine IL-6 and against the endopeptidase MMPs (matrix metalloproteinases) subtype I and II, with highest activity being observed for kaempferol. Hence, M. oleifera seeds could be a promising source of bioactive compounds with potential antioxidant and wound healing capabilities.

Lantana camara L. and Lantana montevidensis Briq. (F. Verbenaceae) are invasive ornamental weeds native to the tropical regions of Africa and America. The leaves of both species have been traditionally used as infusions for treating fever, rheumatism, and cancer. LC–MS–MS-guided profiling of the methanolic extracts of the leaves of L. camara and L. montevidensis growing in Egypt led to the putative identification of 59 compounds belonging to terpenoids, flavonoids, iridoid glycosides, phenolic acids, and their derivatives. The in-vitro antioxidants and anti-inflammatory and anticancer activities of the two extracts were investigated. L. camara and L. montevidensis inhibited DPPH^• (IC₅₀ = 34.01 ± 1.32 and 47.43 ± 1.74 µg/mL), ABTS⁺ (IC₅₀ = 30.73 ± 1.42 and 40.37 ± 1.51 µg/mL), and superoxide anion (IC₅₀ = 1.57 ± 0.19 and 1.31 ± 0.14 μg/mL) free radicals. A potent anti-inflammatory effect was observed for both species through the inhibition of elastase release in fMLF/CB-induced human neutrophils (IC₅₀ = 2.40 ± 0.16 and 1.90 ± 0.07 μg/mL). The extracts showed significant cytotoxic activity against a panel of cancer cell lines with the most potent activity against Caco cells (IC₅₀ = 45.65 ± 1.64 and 40.67 ± 1.52 µg/mL for L. camara and L. montevidensis, respectively). Western blotting supported by FACS analysis revealed that the extracts inhibited cancer cell proliferation, reduced metastasis, and induced apoptosis resulting in cell cycle arrest. This was achieved via increasing mRNA and protein expressions of p53 and GSK-3β as well as decreasing the expression of PI3K, Akt, and cyclin D1.

Species belonging to the Zingiberaceae family are of high nutritional, industrial, and medicinal values. In this study, we investigated the effect of processing steps (fresh vs. dried milled rhizomes) and extraction methodologies (hydrodistillation vs. hexane extraction) of curcuma essential oil on its chemical content (using GC-MS analysis), its antioxidant behavior (using in vitro assays such as DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation), and its enzyme inhibitory activities (on tyrosinase, acetylcholinesterase, butylcholinesterase, α-amylase, and α-glucosidase) supported by multivariate analysis, in silico studies, and molecular dynamics. The GC-MS investigations revealed a high degree of similarity in the chemical profile of fresh hydrodistilled and hexane-extracted essential oils with tumerone and curlone being the major metabolites. The extraction techniques affected the concentrations of other minor constituents such as terpinolene, caryophylla-4(12), 8(13)-dien-5α-ol, and neo-intermedeol, which were almost exclusively detected in the hydrodistilled fresh essential oil; however, zingiberene and β-sesquiphellandrene were predominant in the hexane-extracted fresh essential oil. In the dried curcuma rhizomes, tumerone and curlone contents were significantly reduced, with the former being detected only in the hydrodistilled essential oil while the latter was doubly concentrated in the hexane-derived oil. Constituents such as D-limonene and caryophyllene oxide represented ca. 29% of the dried hydrodistilled essential oil, while ar-turmerone was detected only in the dried hydrodistilled and hexane-extracted essential oils, representing ca. 16% and 26% of the essential oil composition, respectively. These variations in the essential oil chemical content have subsequently affected its antioxidant properties and enzyme inhibitory activities. In silico investigations showed that hydrophobic interactions and hydrogen bonding were the characteristic binding modes of the bioactive metabolites to their respective targets. Molecular dynamics revealed the stability of the ligand-target complex over time. From the current study we conclude that fresh hexane-extracted essential oil showed the best radical scavenging properties, and fresh rhizomes in general display better enzyme inhibitory activity regardless of the extraction technique.

The Asteraceae is a large family, rich in ornamental, economical, and medicinally valuable plants. The current study involves the analytical and pharmacological assessment of the methanolic extracts of three less investigated Asteraceae plants, namely Echinops ritro, Centaurea deflexa, and Tripleurospermum decipiens, obtained by three different extraction methodologies viz. maceration (MAC), ultrasound-assisted extraction (UAE), and homogenizer-assisted extraction (HAE). LC-MS-MS analysis of E. ritro, C. deflexa, and T. decipiens extracts led to the identification of ca. 29, 20, and 33 metabolites, respectively, belonging to flavonoids, phenolic acids, and fatty acids/amides. Although there were significant differences in the quantitative metabolite profiles in the extracts of E. ritro and T. decipiens based on the used extraction method, no significant variation was observed in the extracts of C. deflexa in the three implemented extraction techniques. The antioxidant activities of the nine extracts were assessed in vitro using six different assays viz. DPPH, ABTS, CUPRAC, FRAP, PDA, and metal chelation assay (MCA). The HAE/UAE extracts of E. ritro and the UAE/ MAC extracts of C. deflexa displayed the highest antioxidant activity in the DPPH assay, while the UAE extract of T. decipiens showed the strongest antioxidant activity in both the CUPRAC and MCA assays. The enzyme inhibitory activities of the nine extracts were studied in vitro on five different enzymes viz. tyrosinase, α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinestrase (BChE), affecting various pathological diseases. Concerning C. deflexa, its MAC /UAE extracts showed the strongest inhibition on α-amylase, while its UAE/HAE extracts displayed strong inhibitory power on AChE. However, no significant difference was observed on their effects on tyrosinase or BChE. For T. decipiens, its UAE/HAE showed potent inhibition to α-glucosidase, MAC/ HAE significantly inhibited AChE and BChE, while UAE could strongly inhibit tyrosinase enzyme. For E. ritro, all extracts equally inhibited α-amylase and α-glucosidase, MAC/HAE strongly affected tyrosinase, HAE/MAC best inhibited BChE, while HAE inhibited AChE to a greater extent. Chemometric analysis using PCA plot was able to discriminate between the plant samples and between the implemented extraction modes. The in vitro enzyme inhibitory activities of the extracts were supported by in silico data, where metabolites, such as the lignan arctiin and the flavonoid vicenin-2, dominating the extract of C. deflexa, displayed strong binding to AChE. Similarly, chlorogenic and dicaffeoyl quinic acids, which are some of the major metabolites in the extracts of E. ritro and T. decipiens, bound with high affinity to α-glucosidase.

Brown algae comprise up to 2000 species with wide dissemination in temperate zones. A comprehensive untargeted metabolic profiling guided by molecular networking of three uninvestigated Red-Sea-derived brown algae, namely Sirophysalis trinodis, Polycladia myrica, and Turbinaria triquetra, led to the identification of over 115 metabolites categorized as glycerolipids, fatty acids, sterol lipids, sphingolipids, and phospholipids. The three algae exhibited low-to-moderate antioxidant capacity using DPPH and ABTS assays. Preliminary in vitro antiproliferative studies showed that the algal extracts displayed high cytotoxic activity against a panel of cancer cell lines. The most potent activity was recorded against MCF-7 with IC₅₀ values of 51.37 ± 1.19, 63.44 ± 1.13, and 59.70 ± 1.22 µg/mL for S. trinodis, P. myrica, and T. triquetra, respectively. The cytotoxicity of the algae was selective to MCF-7 without showing notable effects on the proliferation of normal human WISH cells. Morphological studies revealed that the algae caused cell shrinkage, increased cellular debris, triggered detachment, cell rounding, and cytoplasmic condensation in MCF-7 cancer cells. Mechanistic investigations using flow cytometry, qPCR, and Western blot showed that the algae induced apoptosis, initiated cell cycle arrest in the sub-G₀/G₁ phase, and inhibited the proliferation of cancer cells via increasing mRNA and protein expression of p53, while reducing the expression of PI3K, Akt, and mTOR.