Current Bioactive Compounds - Current Issue

Biosurfactants are natural products produced by microorganisms. This study examined the antioxidant activity, biosorption of heavy metals, and stability of lipopeptide biosurfactant (BLA 2906) produced by the Alcaligenes aquatilis bacterium YGD-2906.

Biosurfactant production was determined by using four techniques: hemolytic test, emulsion indices, oil spreading test, and drop collapse test. The biosorption capacity of our biosurfactant to chelate the different heavy metals. The antioxidant activity was evaluated by the reducing power, phosphomolybdate tests, and DPPH•, ABTS^•+ radical scavenging assays and in the end, the stability of this biosurfactant was studied.

A negative hemolytic test, emulsion indices of 63.11% with crude oil, 23.66 mm of oil spreading test, and a positive drop collapse test. The lipopeptide biosurfactant BLA 2906 demonstrated its ability to chelate different heavy metals at pH = 7.2, which gave biosorption capacities of Cu (II), Fe (II), Pb (II), Cd (II), and Zn (II) of 43.34, 43.60, 50.00, 20.08 and 22.48 mg /g of BLA 2906, respectively. The total antioxidant capacity of BLA 2906 presented a value of 0.84 mg Eq Trolox / g DM for the reducing power. On the other hand, the result for the phosphomolybdate test showed a value of 1029.00 ± 3.66 μg / mL to cause a 50% reduction of the reducing activity of the phosphomolybdenum for the BLA 2906. The result of ABTS+• scavenging activity was 10.46%. DPPH radical-scavenging effects and BHA at varying concentrations showed that concentrations required to cause 50% inhibition were 705.48 ± 3.89 µg / ml and 7.61 ± 0.11 µg / ml for this biosurfactant and BHA, respectively. The BLA 2906 showed high stability at different temperatures, pH, and salinity in terms of emulsification activity.

The results obtained by the lipopeptide biosurfactant BLA 2906 are attractive to invest in future applications in different fields such as industry, environment and biotechnology.

The purpose of this research was to determine whether or not Chaturbeeja Churnam (CC) had anti-arthritic properties and the effect it has on Wistar rats that have been induced with arthritis using Complete Freund's Adjuvant (CFA).

Injection of 0.2 milliliters of CFA into the sub-plantar surface of the left hind paw resulted in the development of arthritis. The test samples CC-1 and CC-2 were administered to the animals for a period of 21 days in a row. After the arthritis was induced, the rise in swelling that was noticed was observed. The blood samples that were taken were then used in additional testing with a hematology analyzer to determine the number of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb). Using rat ELISA kits, the levels of IL-6 and TNF- that were found in the serum were also analyzed.

CC showed a significant inhibitory effect in the protein denaturation assay. Results showed that a significant reduction in paw edema was observed in CC-2 treated rats. The maximum anti-inflammatory activity (59.12%) of the CC was noticed at a dose level of 400 mg/kg. The paw edema was restored on day 21 was 4.52 mm for CC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.92 for CC-2 and 1.61 for CC-1. A decrease in levels of RBC and hemoglobin were observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug.

It can be concluded from the study that CC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

In this study, a new series of 2-amino-6-(substituted)pyrimidin-4-yl-2H-chromen-2-one analogues (S1-S15) was prepared by using the Knovengeal condensation method and evaluated for antimicrobial as well as antioxidant activity.

To ensure the progress and confirmation of the reactions, TLC was employed. The melting points (MP) were ascertained utilising a Sunbim-made sonar melting point device produced in India. To confirm the chemical structures of these compounds, we employed a range of techniques, including FT-IR, MS, 1H-NMR, and Elemental analysis. The antimicrobial and antifungal activity was evaluated using the tube dilution method, and a DPPH assay was used to assess antioxidant activity.

Within the series, S1 demonstrated strong antibacterial efficacy against S. aureus, with a minimum inhibitory concentration value of 16.26 µg/ml, while compound S7 displayed significant potential against B. subtilis and E. coli, with a MIC value of 17.34 µg/ml. For antifungal activity, compounds S7 and S11 are the most potent against A. niger, showing a minimum inhibitory concentration of 17.34 µg/ml. In the evaluation of antioxidant activity, it was observed that compounds S2 and S4 displayed outstanding antioxidant properties, with IC50 values of 13.33 µg/ml and 43.13 µg/ml.

The newly created derivatives exhibited robust antimicrobial and antioxidant characteristics upon assessment through designated methodologies, surpassing the efficacy of conventional drugs in the comparative analysis. Notably, compounds S1, S2, S7, S4, and S11 exhibited even greater activity than the reference drugs. Their structure-activity relationship was also discussed.

An investigation on the antioxidant activity and ADME properties of some N-phenylalkanehydrazides (NPhs) in comparison with ascorbic acid was carried out.

The power of the compounds to scavenge the superoxide anion radical was examined using cyclic voltammetry. Furthermore, molecular docking was used to examine how NPhs bind to the antioxidant enzyme glutathione peroxidase (GPx). Finally, ADME properties were predicted using the SwissADME webserver.

The results showed that the studied compounds had significantly higher EC50 values than Vitamin C and displayed spontaneous binding with GPx with binding energy similar to ascorbic acid. Also, substantial values emerged from the predictive analysis of drug-likeness and bioavailability characteristics.

First, the EC50 of the compounds under study was determined by assessing the decrease in the anodic current peak intensity; this demonstrated significant radical scavenging activity. Next, the electrostatic way of binding with ROS radical and with antioxidant enzyme was disclosed by the binding free energies; however, the oxygen and nitrogen atoms in the compounds' structures might make many conventional hydrogen bonds with amino acids. Finally, NPh (a) followed all the rules for drug-likeness and bioavailability estimates, making it a promising moiety for synthesising new antioxidant chemicals.

The current study is a hybrid of experimental and computational methods that complement each other perfectly.

To understand the effectiveness of identified bioactive compounds derived from Syzygium cumini as antibacterial agents against Staphylococcus aureus infections was studied. Antimicrobial resistance (AMR) has put many modern treatments aside and proved ineffective over many human infections. The misuse and inappropriate overuse of antimicrobials in humans have developed drug-resistant pathogens called “superbugs.” Currently, the World is facing a rise in the crisis regarding strategic information and innovation with a novel breakthrough on demand with an efficient, safe, and alternative drug to check severe attacks of AMR. Herbal medicines are now being pipelined with substantial understanding and trials in complete treatment for many AMR infections. This study is an innovative approach that shows constant stability by directly inhibiting the protein involved in cell wall synthesis of the pathogen with the ligand selected on interaction.

i) Elucidating the bidirectional approach of bioactive compounds identified from Syzygium cumini as an alternative drug to control infection caused by AMR Staphylococcus aureus. ii) Molecular dynamics simulation analysis to prove its significance in understanding the mechanism of penicillin-binding protein 2a responsible for cell wall synthesis in AMR Staphylococcus aureus being inhibited by the bioactive compounds more effectively than FDA-approved drugs. iii) The bioactive compounds selected were studied for antibacterial and anti-inflammatory activities.

A molecular docking study was performed using AMdock v1.5.2 with the PBP2a from Staphylococcus aureus. SwissADME v2023 and pass online v2.0 were used to understand the drug-likeness prophecies for these compounds. MD simulations identified Beta-Glucogallin (BEG) and Dihydro Dehydro Coniferyl alcohol (DIH) as hit compounds. Using GROMACS v2020.6, BEG and DIH, identified for molecular dynamics simulation studies, indicated maximum hydrogen bonds. All the results of RMSD, RMSF, SASA, RG, H bonding, and MMPBSA were compared and analyzed with FDA-approved drugs. The phytocompounds present in Syzygium cumini were retrieved from the PubMed database.

Binding affinities for DIH and BEG; -55.202 +/-20.494, and 27.972+/-16.329 with 1MWU respectively. The RMSD (1MWU-APO, 1MWU-MET, 1MWU-BEG and 1MWU-DIH complex proteins were 0.860 +/- 0.04 nm, 0.80 +/- 0.08 nm, 0.56 +/- 0.07 nm, 0.51 +/- 0.10 nm respectively). RMSF (1MWU-APO, 1MWU-MET, 1MWU-BEG and 1MWU-DIH complex proteins were 0.27 +/- 0.14 nm, 0.20 +/- 0.09 nm, 0.29 +/- 0.16 nm, 0.29 +/- 0.14 nm respectively). RG (1MWU-APO, 1MWU-MET, 1MWU-BEG and 1MWU-DIH complex proteins were 3.47 +/- 0.09 nm, 3.45 +/- 0.05, 3.66 +/- 0.04 nm, 3.63 +/- 0.06 nm respectively). SASA (1MWU-APO, 1MWU-MET, 1MWU-BEG and 1MWU-DIH) complex proteins were 312.26 +/- 7.43 nm, 319.68 +/- 4.46, 321.16 +/- 4.85 nm, 338.4 +/- 4.05 nm respectively.

The computational analysis utilized molecular docking and molecular dynamics simulations to evaluate interactions between S. aureus, Penicillin-binding protein 2a (PBP2a), and phytochemical compounds from Syzygium cumini. Among the compounds analyzed, Beta-Glucogallin (BEG) and Dihydro Dehydro Coniferyl alcohol (DIH) exhibited stable binding and interactions, demonstrating potential as antimicrobial agents. PASS software analysis further supported their antibacterial and anti-inflammatory activities, indicating the need for subsequent in vitro and in vivo validation studies. These compounds show promise as leads for drug development efforts to address antimicrobial resistance.

Wogonin, a bioactive compound isolated from S. barbata D. Don, has been identified in the literature as a potential inhibitor of monoamine oxidase (MAO), a key enzyme involved in the degradation of neurotransmitters associated with mood regulation. This study aims to investigate the antidepressant-like activity of wogonin in vivo, utilizing a preclinical model. The rationale for selecting wogonin stems from its documented MAO inhibitory properties, suggesting a potential role in modulating neurotransmitter levels implicated in depressive disorder.

The study employs a multifaceted approach, incorporating behavioural, neurochemical, and biochemical assessments. The Chronic Unpredictable Mild Stress model is utilized to induce depression-like behavior in rodents for 21 days. Two doses of wogonin (20 and 40 mg/kg per orally) and standard (fluoxetine, 20 mg/kg, and imipramine, 15 mg/kg) were administered to albino mice. Behavioural paradigms, including the Tail Suspension Test, Forced Swim Test, and Open Field Test, are employed to assess the impact of wogonin on depressive-like symptoms on the 21^st day. Neurochemical analyses focus on alterations in 5-HT, NE, and DA levels within relevant brain regions, and MAO activity is quantified to ascertain wogonin's potential as an MAO inhibitor on the 22^nd day. Biochemical assessments emphasize wogonin's antioxidant properties and its ability to mitigate oxidative stress, a significant factor in depression pathophysiology. Plasma nitrite levels are measured to elucidate wogonin's impact on nitric oxide signalling. Plasma corticosteroid levels are also quantified to delineate wogonin's effect on the hypothalamic-pituitary-adrenal (HPA) axis, a central regulator of stress response.

Wogonin demonstrates significant antidepressant effects in a dose-dependent manner in the behavioural assessments, showing a marked reduction in depressive-like behaviours across all paradigms. Neurochemical analyses revealed a significant (p £ 0.05) restoration of monoamine neurotransmitter levels in the relevant brain regions as compared to CUMS-induced stress group. Additionally, wogonin exhibits a potent (p £ 0.05) inhibitory effect on MAO activity. Biochemical assessments demonstrate a significant (p £ 0.05) increase in antioxidant capacity and a reduction in oxidative stress markers. Plasma nitrite levels indicate an enhancement of nitric oxide signalling. Corticosteroid levels showed a modulation of the HPA axis, suggesting a regulatory effect on stress response.

This comprehensive study establishes wogonin as a promising MAO inhibitor with notable antidepressant potential. The findings provide crucial insights into its mechanisms of action, indicating a multifaceted approach to alleviating depression. Wogonin's demonstrated efficacy across behavioural, neurochemical, and biochemical parameters presents a strong foundation for further research and development of wogonin-based antidepressant interventions.

The antioxidant fraction of Stevia rebaudiana has important antidiabetic potential, is poorly soluble, and has low stability, which makes its applicability difficult.

In this study, Stevia's fraction was obtained, characterized by Ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS), and microencapsulated with maltodextrin (MDF), gum arabic (GAF), whey protein + maltodextrin (MDWF), and whey protein + gum arabic (GAWF). Then, the following parameters were evaluated: stability and antioxidant capacity over 30 days, physicochemical characteristics, preservation of bioactive compounds by digestion, and in vitro antidiabetic activity.

The microcapsule with gum arabic showed better microencapsulation efficiency, while its version with maltodextrin provided increased solubility. Microencapsulation reduced the humidity and water activity in the microcapsules, except for the microcapsules containing gum arabic. The combination of maltodextrin and whey protein showed greater luminosity and a whiter powder. The microcapsules with maltodextrin and its mixture with gum arabic kept the phenolic compounds stable for 30 days. The microencapsulation with whey protein increased the antioxidant activity after 15 days of the process and during in vitro digestion. All samples showed 96% inhibition of the α-glucosidase enzyme, and only the microcapsule with maltodextrin inhibited α-amylase (58%).

This study showed paramount results so that Antioxidant Stevia Fraction (ASF) can effectively be an adjuvant product to prevent and treat diabetes.

The ethanolic pretreatment of stevia leaves is considered ecologically favorable and increases its yield, purity level, and sensory profile of sweeteners. We investigated the by-product generated so that we can provide a viable and applicable destination to effectively contribute to the production and industrial chain of stevia sweeteners. Recently, an antioxidant and antidiabetic fraction was obtained through stevia methanolic extraction. However, this process is costly, has a low yield, and is non-green. In this study, we got an antioxidant fraction of stevia from its pretreatment by-product, the ethanolic extract, characterized its bioactive compounds - mainly phenolic acids and flavonoids - and evaluated its antidiabetic and anti-lipid capacity.

The ethanolic extract was fractionated, then the ethyl acetate fraction was microencapsulated. Physicochemical, Mass Spectrometry (UHPLC/MS-MS), scanning electron microscopy, microencapsulation efficiency, and antioxidant capacity analyses were carried out. The antioxidant capacity was evaluated. Antihyperglycemic capacity was assessed by inhibition of α-glucosidase and α-amylase. For antilipid potential, inhibition of pancreatic lipase was measured.

Antioxidant potential was observed mainly in the fraction. Microencapsulation improved the stability of the fraction. Mass spectrometry allowed comparison with phenolic and flavonoid compounds from the methanolic and ethanolic fractions of the by-product. Many compounds were coincident, which may explain the similar antioxidant capacity found. The samples showed more than 90% inhibition of alpha-glucosidase, which may indicate potential antidiabetic activity. All samples showed inhibition of the pancreatic lipase enzyme higher than 80%, reaching 91.05% for the free fraction.

This study represented the recovery of a by-product and showed that this antioxidant fraction deserves further investigation for its bioactive potential, especially antioxidant, antidiabetic, and anti-lipid.

Bioactive compounds were isolated, characterized, but their efficacy, potency and mechanism of action to treat/prevent several diseases yet to defined. The present review provides the insight on the activity of nature derived bioactive compounds therapeutic potential against communicable and non-communicable disease by using in silico approaches such as structure-based virtual screening, ligand-based virtual screening, quantitative structure activity relationships (QSAR) modeling, network-based methods (molecular networking) which could be a breakthrough for the novel bioactive drug development of personalized medicine toward the numerous diseases.

This study conducted a thorough literature search on various computational tools used for elucidation of bioactive compounds against communicable and non-communicable diseases. The search was performed using multiple search engines and the main keywords, and only English publications (Web of science, Pub med, Science direct etc.) published up to 2023 were included.

The research presented the various computational tools used for elucidation of bioactive compounds against communicable and non-communicable diseases and possible mechanism of action of lead compounds. It also gives the brief how computational tools might be used in future for personalized medicine development with recently conducted studies outcome.

The present review concludes that computational tools help to narrow down the hit compounds via computational tools (virtual screening) and in short period of the time millions of bioactive compounds could be investigated for their therapeutic potential. These review emphasize the potential impact of computational approaches on drug development and personalized medicine.