Marine-derived natural products are rich source of secondary metabolites with huge potentials including novel therapeutic agents. Marine algae are considered to be a good source of secondary metabolites with versatile bioactivities. During the last few decades, researches related to natural products obtained from brown algae have remarkably escalated as they contain active compounds with varied biologically activities like antimicrobial, anticancer, antioxidant, anti-inflammatory, antidiabetic, and antiparasitic properties. The main bioactive components such as phlorotannin, fucoxanthin, alginic acid, fucoidan, and laminarin have been briefly discussed here, together with their composition and biological activities. In this review, the biological function of extracts and the metabolites of brown algae as well as their pharmacological impacts with the description of the possible mechanism of their action are described and discussed. Also, this study is expected to examine the multifunctional properties of brown algae that facilitate natural algal products, including the ability to integrate these functional properties in a variety of applications.

This study employed green chemistry to synthesize copper nanoparticles (CuNPs) using fresh root extract of Withania somnifera. The size, shape, morphology, and stability of resultant CuNPs were investigated by UV‐Vis spectroscopy, FTIR, transmission electron microscopy (TEM), and energy‐dispersive spectrophotometer. Crude extracts were assessed phytochemically to determine the presence of alkaloids, flavonoids, phenols, saponins, steroids, and tannins. The UV‐Vis absorption spectra show maximum absorption at 330 nm, and FTIR showed the presence of biological molecules responsible for reducing Cu⁺ ions. In TEM and EDS analyses, the average diameter of the synthesized NPs was found to be 6.28 ± 1.13 nm. The crystal structure of synthesized nanoparticle was determined using XRD analysis and showed its peak at 36.34°, 43.33°, 50.47°, and 73.57°, which corresponds to the cubic lattice of copper. The synthesized nanoparticles (NPs) were tested for their in vitro antimicrobial activity against bacterial strains E. coli and S. aureus by the agar well diffusion method which showed higher efficiency against S. aureus. The antioxidant activity of the synthesized NPs was evaluated by DPPH assay, and the percentage of inhibition was found to be 62% at the concentration of 400 μg/ml and the IC50 value was 51.53 μg/ml. The present investigation suggests that the biosynthesized CuNPs showed prominent antibacterial and free radical scavenging potential. The result proved that root extract of W. somnifera could be applied for synthesis of nanoparticle CuNPs with high uniform particle size along with potent biological activity.

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein of the leucine zipper family, which mitigates inflammation and employs cytoprotective effects. Attempting to unravel the epigenetic regulation of type 2 diabetes mellitus (T2DM) and diabetic foot ulcer (DFU), we profiled the expression of eleven isoform-specific histone deacetylases (HDACs) and correlated them with NRF2 and cytokines. This study recruited a total of 60 subjects and categorized into DFU patients (n = 20), T2DM patients (n = 20), and healthy controls (n = 20). The DFU patients were subcategorized into uninfected and infected DFU (n = 10 each). We observed a progressive decline in the expression of NRF2 and its downstream targets among T2DM and DFU subjects. The inflammatory markers IL-6 and TNF-α were significantly upregulated, whereas anti-inflammatory marker IL-10 was significantly downregulated in DFU. Of note, a significant upregulation of HDAC1, 3, 4, 11, SIRT3 and downregulation of HDAC2,8, SIRT1, SIRT2, SIRT3, SIRT7 among DFU patients were observed. The significant positive correlation between NRF2 and SIRT1 in DFU patients suggested the vital role of NRF2/SIRT1 in redox homeostasis and angiogenesis. In contrast, the significant negative correlation between NRF2 and HDAC1, 3 and 4, implied an imbalance in NRF2-HDAC1, 3, 4 circuit. Furthermore, a significant positive correlation was observed between HDAC4 and IL-6, and the negative correlation between SIRT1 and IL-6 suggested the pro-inflammatory role of HDAC4 and the anti-inflammatory role of SIRT1 in NRF2 signaling. In conclusion, the epigenetic changes such as upregulation of HDAC1, 3, 4, 11, SIRT3 and downregulation of HDAC2, 8, SIRT1, SIRT2, SIRT6, SIRT7 and their association with NRF2 as well as inflammatory markers are suggestive of their roles in pathophysiology of T2DM and DFU.

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a stress-activated transcription factor regulating antioxidant genes, and a deficiency thereof, slowing lymphangiogenesis, has been reported in diabetic foot ulcer (DFU). The mode of Nrf2 regulation in DFU has been less explored. Emerging studies on miRNA-mediated target regulation show miRNA to be the leading player in the pathogenesis of the disease. In the present study, we demonstrated the role of miR-27b in regulating Nrf2-mediated angiogenesis in DFU. A lower expression of mRNA targets, such as Nrf2, HO-1, SDF-1α, and VEGF, was observed in tissue biopsied from chronic DFU subjects, which was in line with miR-27b, signifying a positive correlation with Nrf2. Similarly, we found significantly reduced expression of miR-27b and target mRNAs Nrf2, HO-1, SDF-1α, and VEGF in endothelial cells under a hyperglycemic microenvironment (HGM). To confirm the association of miR-27b on regulating Nrf2-mediated angiogenesis, we inhibited its expression through RNA interference-mediated knockdown and observed disturbances in angiogenic signaling with reduced endothelial cell migration. In addition, to explore the role of miR-27b and angiogenesis in the activation of Nrf2, we pretreated the endothelial cells with two well-known pharmacological compounds—pterostilbene and resveratrol. We observed that activation of Nrf2 through these compounds ameliorates impaired angiogenesis on HGM-induced endothelial cells. This study suggests a positive role of miR-27b in regulating Nrf2, which seems to be decreased in DFU and improves on treatment with pterostilbene and resveratrol.

Visfatin has been reported as a risk factor and a potential diagnostic marker in cancer. It is an adipokine, secreted by visceral fat and associated with the pathogenesis of arterial hypertension. We investigated the circulatory levels of visfatin in hypertensive patients with hypertriglyceridemia, which are the risk factors for various cancers and its association with proinflammatory cytokines. A total of 81 (male/female: 33/48) subjects with or without hypertension were enrolled for this study. Group 1 was normotensive, Group 2 hypertensive, and Group 3 with hypertension with hypertriglyceridemia. Data on anthropometric and biochemical data were recorded. Plasma visfatin levels were measured using an ELISA kit. The plasma inflammatory cytokines were estimated using a multiplex bead‐based assay. The results revealed that the hypertension with hypertriglyceridemia group has the highest levels of visfatin compared to the hypertension and control groups with a significant difference (p < 0.001). Besides, circulatory visfatin showed the strongest possible correlation with proinflammatory cytokines among hypertensive patients with hypertriglyceridemia. We found a positive correlation between visfatin and diastolic blood pressure as well as high‐density lipoproteins. In conclusion, the outcomes of the present study demonstrate that plasma visfatin levels were found to be elevated in hypertensive patients with hypertriglyceridemia and associated with proinflammatory cytokines. Since hypertension has been documented as the most common comorbidity observed in cancer patients, visfatin may be a novel potential therapeutic target for hypertension in cancer patients and survivors.

Background. The regulation of vascular endothelial growth factor (VEGF) by genetic factors in T2DM and DFU still requires thorough investigation. Hence, the present study aimed to investigate the association of VEGF +405 G/C in DFU subjects and correlate it with its circulatory levels, infection severity, and amputation rate. Materials and Methods. This study registered a total of 754 participants of which group I: healthy controls (n = 297), group II: T2DM subjects (n = 242), and group III: DFU subjects (n = 215). Genotyping and levels of rs2010963 were analyzed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and ELISA, respectively. Results. Results of the current study showed a clear decline in circulatory VEGF‐A levels in DFU subjects. VEGF‐A was decreased in DFU subjects with the mutant “CC” genotype. The mutant “CC” of VEGF +405G/C was also found to be more susceptible to ulcer grade (III and IV) and major amputations. Conclusion. VEGF +405G/C SNP is associated with levels, infection severity, and amputation amongst South Indian DFU patients.