Bio-Stimulant for Improving Simmondsia chinensis Secondary Metabolite Production, as Well as Antimicrobial Activity and Wound Healing Abilities.

Simmondsia chinensis is a dioecious, long-lived perennial shrub. Its leaves contain several antioxidant flavonoids that have numerous pharmacological effects. Various strategies have been explored to propagate jojoba with enhanced pharmacological values. This research evaluates the bio-stimulatory impacts of He-Ne laser seed irradiation on seed germination, plantlet growth, and alteration of the composition and bioactivities of phytochemicals in jojoba plants. Jojoba seeds were irradiated for 5, 10, and 15 min before in vitro germination. Germination, growth, and multiplication parameters were recorded during germination, multiple-shoot induction, and rooting stages. The wound healing and antimicrobial activities of methanolic extracts from plant lines obtained from the non-irradiated (control) and 10 min irradiated seeds were compared by excision wound model in Wistar male rats and zone of inhibition assay. Our study revealed that laser irradiation increased seed germination, with the highest percentage observed in seeds irradiated for 10 min. Plant lines from the 10 min irradiated seeds produced more explants with higher explant heights and numbers of leaves, more roots, and higher photosynthetic pigment contents than those of control and other laser testings. By comparing plant extracts from the control and 10 min treatments, we observed that extracts from the 10 min treatment exhibited higher percentages of wound contraction and shorter epithelialization periods. In addition, these extracts also resulted in higher levels of angiogenesis elements (VEGF, TGF-ß1, and HIF-1α) and reduced the inflammation regulators (IL-1ß, IL-6, TNF-α, and NFκB) in the experimental rats. In concordance, extracts from the 10 min treatment also explained raised antibacterial activities towards Staphylococcus aureus and Escherichia coli. Our findings show that pre-sowing seed treatment with a He-Ne laser (632.8 nm) could be a good technique for stimulating S. chinensis plant growth and increasing the impact compound levels and biological activities.

Zerumbone Exhibit Protective Effect against Zearalenone Induced Toxicity via Ameliorating Inflammation and Oxidative Stress Induced Apoptosis.

Zearalenone are widely occurring food contaminants that cause hepatotoxicity. This research work aimed to investigate how zerumbone, a plant-derived dietary compound, can fight ZEA-induced hepatotoxicity. ZER is found to increase the cells' toxin resistance. This study was performed on mice challenged with ZEA. The administration of ZER decreased the level of alkaline phosphatase and alanine aminotransferase (ALT). Simultaneously, ZER attenuated the inflammatory response via significantly reducing the levels of pro-inflammatory factors, including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) in serum. Pretreatment with ZER reduced the hepatic malondialdehyde (MDA) concentration, as well as the depletion of hepatic superoxide dismutase (SOD), hepatic glutathione (GSH), and hepatic catalase (CAT). Moreover, it significantly ameliorated ZEA-induced liver damage and histological hepatocyte changes. ZER also relieved ZEA-induced apoptosis by regulating the PI3K/AKT pathway and Nrf2 and HO-1 expression. Furthermore, ZER increasingly activated Bcl2 and suppressed apoptosis marker proteins. Our findings suggest that ZER exhibits the ability to prevent ZEA-induced liver injury and present the underlying molecular basis for potential applications of ZER to cure liver injuries.

Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway.

Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes' exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin's activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells' (HUVECs') signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants' intracellular concentrations. These were effectively antagonized with MGN (20 µM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity.

Thidiazuron suppresses breast cancer via targeting miR-132 and dysregulation of the PI3K-Akt signaling pathway mediated by the miR-202-5p-PTEN axis.

Chemo-resistance and metastasis are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator (phytohormone) whose biological effects on humans and animals has not yet been determined. In this study, we investigated the anticancer activity of this phytohormone on the drug resistant-triple negative breast cancer cell line MDA-MB-231. Treatment of the breast cancer cells with TDZ (1-50 µmol/L) caused more stressful environment and induced a significant increase in active caspase-positive cells. In addition, TDZ treatment (5 and 10 µmol/L) significantly attenuated the migration and the invasiveness of these highly metastatic cancer cells. Mechanistically, TDZ reduces cancer progression and invasiveness by targeting miR-202-5p, which stimulates the expression of phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates the PI3K-Akt signaling pathway. Treatment with TDZ significantly upregulates miRNA-132, the suppressor of breast cancer proliferation, which is also implicated in dysregulation of the TEN-Akt-NFκB signaling pathway. Interestingly, our molecular docking analysis revealed a potential non-covalent interaction between TDZ and Akt, PTEN, and PI3K. These findings suggest that TDZ suppresses breast cancer metastasis by targeting miRNA-132, the miR-202-5p-PTEN axis, and the PI3K-Akt signaling pathway downstream.