Fabrication of Curcumin-Based Electrochemical Nanosensors for the Detection of Environmental Pollutants: 1,4-Dioxane and Hydrazine.

This work reports the development of novel curcuminoid-based electrochemical sensors for the detection of environmental pollutants from water. In this study, the first set of electrochemical experiments was carried out using curcumin-conjugated multi-walled carbon nanotubes (MWCNT-CM) for 1,4-dioxane detection. The MWCNT-CM/GCE showed good sensitivity (103.25 nA nM-1 cm-2 in the linear range 1 nM to 1 µM), with LOD of 35.71 pM and LOQ of 108.21 pM. The second set of electrochemical experiments was carried out with bisdemethoxy curcumin analog quantum dots (BDMCAQD) for hydrazine detection. The BDMCAQD/GCE exhibited good sensitivity (74.96 nA nM-1 cm-2 in the linear range 100 nM to 1 µM), with LOD of 10 nM and LOQ of 44.93 nM. Thus, this work will serve as a reference for the fabrication of metal-free electrochemical sensors using curcuminoids as the redox mediator for the enhanced detection of environmental pollutants.

microRNAs and their therapeutic strategy in phase I and phase II clinical trials.

miRNAs play a crucial therapeutic role in diseases such as cancer, diabetes and viral infections, with around 1900 identified in the human genome. Some have progressed to clinical trials, and miRNA mimics and miRNA inhibitors are pivotal therapeutic molecules undergoing evaluation. The review delves into various miRNA-associated clinical trials, emphasizing their precision in targeting specific genes, modulating disease pathways and diagnostic potential. This underscores the importance of miRNA therapy, foreseeing innovations in precision medicine techniques for diverse diseases. The future envisions improved delivery systems addressing challenges like immunogenicity and digestion, while a comprehensive miRNA-based omics database could guide the development of tailored antisense miRNAs, further advancing precision medicine strategies.

In-vivo anti-hyperglycemic effect of herbal extracts Tribulus terrestris (L) and Curcuma amada (R) on streptozotocin-induced diabetic rats and its associated histopathological studies.

Dia/betes is a serious health concern in many countries with high blood glucose, obesity, and multiple organ failures in late stages. Treating diabetes with effective drugs is still a challenging issue since most of the available diabetic drugs are not effective in combating diabetes, especially in secondary disease complications like obesity, retinopathy, and nephropathy associated with diabetes. Hence search for effective antidiabetic medication, especially from natural sources is mandatory with no adverse side effects. In the present study, a combined herbal aqueous extract of Tribulus terrestris and Curcuma amada was administered to diabetic-induced rats for 37 days. During experimentation, the mean blood glucose level was estimated and at the end of the experiment on the 37th day, the animal was sacrificed and observed for weight gain, plasma insulin, glycogen, glycated hemoglobin, urea, and creatinine level. The results revealed that TT and CA extract-treated diabetic groups significantly lowered the mean blood glucose level followed by increased glycogen and insulin level. Urea, creatinine, and HbA1c levels were considerably reduced in TT and CA-treated diabetic animals as compared to that of antidiabetic drug Glibenclamide-treated groups. TT and CA-treated diabetic animals showed considerable net body weight gain at the end of the experimental day. A concluding remark of the study shows that TT and CA herbal extract is effective against diabetes and it can be considered as an antidiabetic agent in ayurvedic medicine practice.

Insight into the Inhibitory Mechanisms of Hesperidin on α-Glucosidase through Kinetics, Fluorescence Quenching, and Molecular Docking Studies.

The α-glucosidase inhibitor is of interest to researchers due to its association with type-II diabetes treatment by suppressing postprandial hyperglycemia. Hesperidin is a major flavonoid in orange fruit with diverse biological properties. This paper evaluates the effects of hesperidin on α-glucosidase through inhibitory kinetics, fluorescence quenching, and molecular docking methods for the first time. The inhibition kinetic analysis shows that hesperidin reversibly inhibited the α-glucosidase activity with an IC50 value of 18.52 µM and the inhibition was performed in an uncompetitive type. The fluorescence quenching studies indicate that the intrinsic fluorescence of α-glucosidase was quenched via a static quenching process and only one binding site was present between the hesperidin and α-glucosidase. The interaction between them was spontaneous and mainly driven by hydrogen bonds, as well as hydrophobic forces. Furthermore, the molecular docking results suggest that hesperidin might bond to the entrance or outlet part of the active site of α-glucosidase through a network of five hydrogen bonds formed between hesperidin and the four amino acid residues (Trp709, Arg422, Asn424, and Arg467) of α-glucosidase and the hydrophobic effects. These results provide new insight into the inhibitory mechanisms of hesperidin on α-glucosidase, supporting the potential application of a hesperidin-rich orange product as a hypoglycemic functional food.

Design of Balanced Cyclooxygenase Inhibitors Based on Natural Anti-inflammatory Ascidian Metabolites and Celecoxib.

The serious adverse effects caused by non-selective and selective cyclooxygenase-2 (COX-2) inhibitors remain significant concerns for current anti-inflammatory drugs. In this study, we present the design and synthesis of a novel series of celecoxib analogs incorporating a hydrazone linker, which were subjected to in silico analysis to compare their binding poses with those of clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) against COX-1 and COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX enzymes, and compound 6 m, exhibiting potent balanced inhibition, was selected for subsequent in vitro anti-inflammatory assays. Treatment with 6 m effectively suppressed the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, resulting in reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, as well as decreased production of prostaglandin E2 (PGE2 ), nitric oxide (NO), and reactive oxygen species (ROS). However, 6 m has no effect on the MAPK signaling pathway. Therefore, due to its potent in vitro anti-inflammatory activity coupled with lack of cytotoxicity, 6 m represents a promising candidate for further development as a new lead compound targeting inflammation.

Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach.

Introduction: Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties. Methods: An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening. Results: Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00µm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain. Discussion: We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

A Chemo-Enzymatic Approach for Preparing Efinaconazole with High Optical Yield.

Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing efinaconazole (7), a clinically used antifungal agent. This method involves utilizing benzaldehyde lyase (BAL) to catalyze the crucial benzoin condensation step in the ketone precursor. Treating 2,4-difluorobenzaldehyde with BAL in the presence of thiamin-diphosphate (ThDP) and Mg2+ resulted in the formation of α-hydroxy ketone which then underwent the preparation of 7. This innovative approach not only provides a greener alternative but also offers significant advantages over the traditional chemical process. Through our efforts and development work, we have established efficient and scalable procedures that enable the production of 7 in a moderate 38% yield.

Linoleic acid from the endophytic fungus Diaporthe sp. HT-79 inhibits the growth of Xanthomonas citri subsp. citri by destructing the cell membrane and producing reactive oxygen species (ROS).

Citrus canker disease caused by Xanthomonas citri subsp. citri (Xac) severely influences the quality and quantity of citrus fruits. The current management of this disease mainly relies on the application of copper-associated chemicals, which poses a threat to human health and the environment. The present study isolated an endophytic fungus HT-79 from the healthy navel orange tree, whose crude fermentation product significantly inhibited the growth of Xac. The strain HT-79 was identified as a species of the Diaporthe genus. The petroleum ether extract (PEE) of the crude fermentation product of HT-79 exhibited remarkable activity against Xac with a MIC (minimum inhibitory concentration) value of 0.0625 mg/mL, significantly better than the positive control CuSO4 (MIC = 0.125 mg/mL). Bioassay-guided isolation of PEE resulted in the discovery of one highly potent anti-Xac subfraction, namely fraction 5 (MIC = 0.0156 mg/mL). Gas chromatography-mass spectrometry (GC-MS) analysis revealed that fraction 5 mainly consisted of palmitic acid (18.17%), ethyl palmitate (15.66%), linoleic acid (6.80%), oleic acid (18.32%), ethyl linoleate (21.58%), ethyl oleate (15.87%), and ethyl stearate (3.60%). Among these seven compounds, linoleic acid (MIC = 0.0078 mg/mL) was found to be the most potent against Xac, followed by oleic acid (MIC = 0.0156 mg/mL), while all others were less pronounced than CuSO4. Linoleic acid highly inhibited the growth of Xac via the destruction of the cell membrane and overproduction of reactive oxygen species (ROS). A preliminary in vivo experiment revealed that linoleic acid was effective in the control of citrus canker disease.

Pomelo seed oil: Natural insecticide against cowpea aphid.

Cowpea aphid (Aphis craccivora Koch) is a plant pest that causes serious damage to vegetable crops. Extensive use of synthetic chemical pesticides causes deleterious effects on consumers as well as the environment. Hence, the search for environmentally friendly insecticides in the management of cowpea aphids is required. The present work aims to investigate the aphicidal activity of pomelo seed oil (PSO) on cowpea aphids, the possible insecticidal mechanisms, its chemical constituent profile, as well as the toxicity of its primary compounds. The results of the toxicity assay showed that PSO had significant insecticidal activity against aphids with a 72-hour LC50 value of 0.09 µg/aphid and 3.96 mg/mL in the contact and residual toxicity assay, respectively. The enzymatic activity of both glutathione S-transferase (GST) and acetyl cholinesterase (AChE) significantly decreased, as well as the total protein content, after PSO treatment, which suggested that the reduction of AChE, GST, and the total protein content in aphids treated with PSO might be responsible for the mortality of A. craccivora. The GC-MS analysis revealed that PSO contained limonene (22.86%), (9Z,12Z)-9,12-octadecadienoic acid (20.21%), n-hexadecanoic acid (15.79%), (2E,4E)-2,4-decadienal (12.40%), and (2E,4Z)-2,4-decadienal (7.77%) as its five major compounds. Furthermore, (9Z,12Z)-9,12-octadecadienoic acid showed higher toxicity to aphids than both PSO and thiamethoxam (positive control). This study emphasized the potential of PSO as a natural plant-derived insecticide in controlling cowpea aphids and also provided a novel approach for the value-added utilization of pomelo seed.

Variations of Bioactive Phytochemicals and Antioxidant Capacity of Navel Orange Peel in Response to Different Drying Methods.

The effects of five different drying methods, namely, freeze drying (FD), shade drying (SD), hot-air oven drying at 50 °C (OD50), 70 °C (OD70), and microwave drying (MD) on the bioactive phytochemicals and antioxidant capacity of navel orange peel were assessed and comprehensively discussed in detail. Compared with other drying methods, MD-treated peel contained the lowest total phenolic content (TPC) and total flavonoid content (TFC). The peel subjected to OD70 treatment was superior in TPC relative to other treatments and the highest TFC was found in the peels treated with FD. HPLC analysis identified thirteen flavonoids involving three flavanone glycosides (FGs) and ten polymethoxyflavones (PMFs) in navel orange peel and revealed that PMFs in peel were stable under all these drying methods, whereas the three major FGs (narirutin, hesperidin, and didymin) in peel significantly degraded in response to MD treatment. The peels subjected to OD50/OD70 treatments had the most potent antioxidant capacity when compared to other drying methods. Furthermore, Pearson's correlation analysis was performed. The results revealed here allow us to recommend the use of OD50 or OD70 for the drying of orange peel, both of which help the maintenance of bioactive compounds in the peel and improve its antioxidant capacity.

Anti-inflammatory activity of the water extract of Semiliquidambar cathayensis leaf.

In this study, the anti-inflammatory effect of the water extract of Semiliquidambar cathayensis leaf (WESCL) was evaluated for the first time. WESCL exhibited anti-inflammatory activity by significantly reducing the cell metamorphosis, the production of nitric oxide (NO), and reactive oxygen species (ROS) in LPS-stimulated RAW 264.7 macrophages while showing no cytotoxic effect to the cells. Furthermore, an in vivo study revealed that WESCL could alleviate the disease development of osteoarthritis (OA) and decrease the level of interleukin-6 (IL-6) in mice. Chemical composition analysis indicated that WESCL contained high amounts of phenolic compounds, flavonoids, and triterpenoid saponins, with the total content being 30.6 mg gallic acid equivalent (GAE)/g, 38.2 mg quercetin equivalent (QE)/g, 100.5 mg oleanolic acid equivalent (OAE)/g, respectively. The present study successfully identified WESCL as a naturally-occurring anti-inflammatory agent, supporting its potent application for the treatment of inflammation-related diseases.

Evaluation of Aspergillus aculeatus GC-09 for the biological control of citrus blue mold caused by Penicillium italicum.

Blue mold caused by Penicillium italicum is a severe postharvest disease in citrus fruits. In this study, the fermentation product (FP-E) of Aspergillus aculeatus GC-09, an endophytic fungus isolated from a citrus plant, was found to exhibit antifungal activity against P. italicum with a MIC of 0.3125 mg/mL. The fungus A. aculeatus GC-09 was identified based on the studies of morphology and ITS nucleotide sequence. FP-E significantly inhibited the spore germination and mycelial growth of P. italicum. Scanning electron microscopy (SEM) results of P. italicum treated with FP-E showed shrunken, distorted and collapsed hyphae and conidiospores, indicative of the cell membrane damage, which was further confirmed by the propidium iodide (PI) fluorescent staining analysis. Consistent with the microscopy observation, FP-E led to the leakage of cellular constituents from P. italicum, which is evident from the increase in electrical conductivity and nucleic acid contents in the mycelial solution incubated with FP-E. In addition, FP-E treatment considerably increased the intracellular reactive oxygen species (ROS) content, and reduced the enzyme activities of both catalase (CAT) and peroxidase (POD) in P. italicum cells. Furthermore, orange fruits treated with FP-E showed fewer disease symptoms compared to the untreated fruits. These results suggested that the antifungal activity of FP-E might be associated with the disruption of cell membrane integrity, the accumulation of ROS level, and the reduction of the antioxidant enzymes activity of P. italicum. Therefore, A. aculeatus GC-09 might be a potential microbial resource for the biocontrol of citrus postharvest blue mold.

Antifungal fatty acid derivatives against Penicillium italicum from the deep-sea fungus Aspergillus terreus SCSIO 41202.

The present work reports the bioassay-guided isolation of four bioactive fatty acid derivatives involving a new butenolide, namely sinulolide I (1) together with three known metabolites (2-4) from the deep-sea sediment derived fungus Aspergillus terreus SCSIO 41202. The chemical structure of compound 1 was elucidated based on extensive spectroscopic methods (1D/2D NMR and HR-ESI-MS), optical rotation and circular dichroism analyses, while the structures of the known compounds (2-4) were established by comparison of NMR spectral data with those reported in literature. All of these four compounds (1-4) exhibited significant antifungal activity against citrus postharvest pathogen Penicillium italicum (MICs around 0.031-0.125 mg/mL).

Structurally diverse secondary metabolites from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001 and their biological evaluation.

Five new compounds, including a cytotoxic dimeric isocoumarin, bipenicilisorin (1), a merosesquiterpenoid, yaminterritrem C (2), a citrinin dimer, penicitrinone F (3), a alkaloid, terremide D (4), and a δ-valerolacton, (E)-4-(propen-1-yl)-5,6-dihydro-2H-pyran-2-one (5), along with ten known compounds (6-15) were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Their structures and absolute configurations were elucidated by NMR spectra, MS, CD, optical rotation, X-ray crystallography, and compared with literature data. Biological evaluation results revealed that 1 exhibited significant cytotoxic activities against K562, A549, and Huh-7 cell lines with IC50 values of 6.78, 6.94, and 2.59µM, respectively. Compound 3 exhibited moderate inhibitory activity against EV71 with IC50 value of 14.50µM. In addition, 13 and 14 showed specific COX-2 inhibitory activities with IC50 values of 1.09 and 1.97µM, respectively.

Chrysamides A-C, Three Dimeric Nitrophenyl trans-Epoxyamides Produced by the Deep-Sea-Derived Fungus Penicillium chrysogenum SCSIO41001.

Three dimeric nitrophenyl trans-epoxyamides, chrysamides A-C (1-3), were obtained from the deep-sea-derived fungus Penicillium chrysogenum SCSIO41001. Their structures were characterized by spectroscopic analysis, electronic circular dichroism computations, and X-ray single-crystal diffraction analysis. Notably, compound 1 possesses a novel centrosymmetric dimer skeleton featuring an unprecedented 7-oxa-2,5-diazabicyclo[2.2.1]heptane ring system, which represents the first example of dimeric nitrophenyl trans-epoxyamide in nature. Compound 3 suppresses the production of proinflammatory cytokine interleukin-17. A possible biosynthetic pathway of 1-3 was proposed.