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Abstract The Red Sea is one of the maximum crucial marine spots comprising excessive biodiversity. This study focuses on the phytochemical and biological biodiversity of marine algae extracts. According to review of literature, 944 phytochemicals were detected in the studied marine algae with great phytochemical and biological biodiversity. Chemical and biological screening of selected marine algae Chapter I HS-GCMS analysis of Padina pavonica and Dictyopteris acrostichoides Padina pavonica and Dictyopteris acrostichoides are two marine algae belong to the same botanical order, and family and were collected at the same time from the same area. Significant biodiversity in their volatile organic composition was found using HS-GCMS. 24 Metabolites were detected in Padina pavonica and 23 metabolites were detected in Dictyopteris acrostichoides. Chapter II Halimeda opuntia and Padina pavonica extracts improve growth and metabolic activities in maize under soil‑saline conditions. Application of Halimeda opuntia and Padina pavonica as algal biofertilizers enhanced the growth characters and other biochemical contents of maize which was exposed to saline conditions at the vegetative stage. The foliar treatment with each algal extract significantly increased the fresh and dry weight of root and shoot, and improved the potassium, chlorophyll a, chlorophyll b and carotenoids contents compared to the control (untreated stressed plants), especially with Padina pavonica extract. Generally, sodium, carbohydrates and proline contents were decreased, while protein, phenols and alkaloids were increased in treated plants in comparison with untreated maize plants. LC-HR-ESIMS analysis revealed the presence of phytoconstituents such as phytohormones, phenolic derivatives, and carotenoids which play an important role in growth promotion. Chapter III Antibiofilm activity of the ethanol extract from marine algae Padina pavonica: An in vitro and in silico study prospective quorum sensing inhibitory activity Biologically guided phytochemical screening of Padina pavonica, Dictyopteris acrostichoides, Turbinaria ornata, Sargassum sanyaense, Halimeda opuntia and Caulerpa racemose indicated that the ethanol extracts exhibited varying antibiofilm activity against the studied Pseudomonas aeruginosa clinical isolates. Padina pavonica and Sargassum sanyaense extracts have a synergistic effect with ceftriaxone against Staphylococcus aureus as MIC of ceftriaxone decreased by two folds when combined with extracts of Padina pavonica or Sargassum sanyaense (from 128 to 32 µg/ml). Ceftriaxone MIC of gram-negative bacteria decreased by one-fold when combined with extracts of Padina pavonica or Sargassum sanyaense. Other extracts have no synergistic or antagonistic effects with antibiotics. Docking of the twenty-seven identified metabolites in Padina pavonica as inhibitors of the quorum-sensing dependent virulence gene engaged. Squalene showed the highest and higher S-score binding energy. Chapter IV Metabolite profiling of green algae Halimeda opuntia to target hepatitis C virus-796 Polymerase inhibitors assisted by molecular docking. The Anti-HCV activities of the six marine algae were tested. Results reveal that Halimeda opuntia, Dictyopteris acrostichoides, and Sargassum sanyaense ethanol extracts have anti-HCV activity, IC50= 7.14, 9.49, and 13.36 µg/mL, respectively. While the other three marine algae ethanol extracts displayed no anti-HCV activity. Metabolic profiling of Halimeda opuntia ethanol extract characterized fifteen metabolites, which were explored against HCV-796, the HCV polymerase Inhibitor, using an in-silico approach via molecular docking. Interestingly 4,9-Diacetoxtudoteal confirmed considerable interaction energies and formed substantial interactions HCV-796 binding site. Chapter V EGFR, and VEGFR inhibitory activity of the crude extract from marine algae Dictyopteris acrostichoides supported by in silico analysis and metabolic profiling. The cytotoxic activity of the six marine algae were tested. The obtained results revealed that the ethanol extracts of Dictyopteris acrostichoides, Padina pavonica, and Sargassum sanyaense had promising cytotoxicity activities against HepG2, MCF-7, and Caco-2 cell lines while the other three marine algae ethanol extracts displayed no cytotoxic activity. Results demonstrated that Dictyopteris acrostichoides ethanol extract displayed cytotoxicity against HepG2, MCF-7, and Caco-2 (IC50= 11.65, 9.28, and 16.86 µg/mL, respectively) compared to doxorubicin as a positive control, (IC50= 5.72, 5.17 and 5.81µg/mL, respectively). Furthermore, the ethanol extract of Dictyopteris acrostichoides was tested against EGFR (IC50= 0.11 µg/mL) compared to lapatinib as a positive control, (IC50= 0.03µg/mL) and against VEGF (IC50= 0.276 µg/mL) compared to sorafenib as a positive control, (IC50= 0.049µg/mL). Seventeen metabolites were identified from the ethanol extract of D. acrostichoides using LC-HR-ESIMS for dereplication purposes. The relationship between the identified compounds and interactions with EGFR and VEGF binding sites in the cancer cell receptors was studied. Interestingly, 1-(3-oxo-undecyldisulfanyl)-undecan-3-one and di(3-acetoxy-5-undecenyl) disulfide confirmed considerable interaction energies and formed substantial interactions EGFR binding site. Interestingly, di(3-acetoxy-5-undecenyl) disulfide confirmed considerable interaction energies and formed substantial interactions VEGFR binding site. Chapter VI Evaluation of Hepatoprotective, nephroprotective and testicular protective activities of the crude extract from marine algae The current study revealed that Sargassum sanyaense could be considered a potentially therapeutic substance due to its ability to prevent testes, hepatic and renal injury with significant anti-inflammatory and antioxidant properties, which may be attributed to the presence of key complementary phytoconstituents. Significant increase in liver enzymes, oxidative stress biomarkers, and inflammatory mediators (MDA, AST, ALT, ALP, ALB, total bilirubin, 8-OHdG, CASP-3, TNF-α) in hepatocytes in CCl4-treated group compared to the normal animals. Likewise, CCl4 administration has depleted the antioxidant protective enzymes in the liver and serum, such as SOD and GSH, compared to the normal control group. While Pretreatment with 100mg/kg algae extracts significantly reduced the liver enzymes, oxidative stress biomarkers, and inflammatory mediators compared to the CCl4-treated animals. Histopathological examination of the liver tissue showed that the most hepatoprotective extracts were Padina pavonica and Sargassum sanyaense. At the same time, congestion of the portal blood vessels was detected with Dictyopteris acrostichoides, Turbinaria ornata, Halimeda opuntia, and a minimal degree of congestion was identified in Caulerpa racemose extract. Kidney oxidative stress, enzymes, and inflammatory mediators (MDA, serum urea levels, serum creatinine levels, 8-OHdG, CASP-3, and TNF-α ) were significantly increased in the CCl4-treated group compared to the normal group, and Padina pavonica, Dictyopteris acrostichoides, Turbinaria ornata, Sargassum sanyaense and Caulerpa racemose extracts pretreated groups. Moreover, CCl4 administration has depleted the antioxidant protective enzymes in the kidney, such as SOD and GSH, compared to the normal control group and Padina pavonica, Dictyopteris acrostichoides, Turbinaria ornata, Sargassum sanyaense, and Caulerpa racemose extracts pretreated groups. Histopathological screening of the kidney tissue showed the nephroprotective effects of extracts Padina pavonica and Sargassum sanyaense, while congestion of the renal blood vessels with mild congestion were detected with Dictyopteris acrostichoides, Turbinaria ornata, Halimeda opuntia, and Caulerpa racemose while significant changes of hematobiochemical parameters and disruptions of kidney structures with the group treated with Halimeda opuntia extract. Plasma gonadotrophins and testosterone disrupted in the CCl4 group. 8-OHdG, CASP-3, and TNFα were significantly increased in testicular tissues in the CCl4-treated group relative to the normal, and 100mg/kg Padina pavonica, Dictyopteris acrostichoides, Turbinaria. ornata, Sargassum sanyaense, and Caulerpa racemose extracts pretreated groups. At the same time, CCl4 administration has depleted the antioxidant protective enzymes in testicular tissues, such SOD and GSH, compared to the normal control group and Padina pavonica, Dictyopteris acrostichoides, Turbinaria ornata, Sargassum sanyaense and Caulerpa racemose extracts pretreated groups. Histopathological screening of the testicular tissue showed testicular protective activity of Sargassum sanyaense extract and promoted recovery toward a normal state. Halimeda opuntia extract exhibited the lowest testicular protective activity, while 100mg/kg Padina pavonica, Dictyopteris acrostichoides, Turbinaria ornate, and Caulerpa extracts exhibited moderate testicular tissue changes. Therefore, this alga could be considered as a new hepatoprotective, nephroprotective, testicular protective, anti-inflammatory, and antioxidant natural drug because of its wide safety margin and relatively few side effects. The mechanism of hepatoprotection, nephroprotective, and testicular protection may be due to the modulation of the antioxidant enzyme systems. These beneficial effects may be attributed to the individual or combined action of the phytochemicals present in the extracts, such as polyphenolic compounds and diterpenes. |