Curative Effects of Triphala Extract against Swim Stress-Induced Gastric Ulcers via Reduced Ulcer Index, Strengthened Gastric Mucosa and Improved Redox State in Rats

Recently, the percentage of Peptic ulcer disease not linked to either Helicobacter pylori or non-steroidal anti-inflammatory drugs has increased and signifies the prominent role of psychophysiological stress in the establishment and advancements of gastric ulcers and other peptic ulcer diseases. The current study was intended not only to develop post-treatment swim stress-induced peptic ulcer disease rat model but also to analyze the curative effects of hydro-alcoholic extract of Triphala in swim stress-induced peptic ulcer disease model. A post-treatment swim stress-induced peptic ulcer disease rat model was developed followed by therapeutic intervention of hydro-alcoholic extract of Triphala. The gross evaluation of gastric tissues showed that swim stress induces significant gastric ulcers in rats that could clearly be observed after 21 d of self-healing. Further, the findings of our interventional investigations revealed that hydro-alcoholic extract of Triphala exerts significant gastro-protective activity in swim stress-induced peptic ulcer disease via decreasing the ulcer index and increasing the protective gastric mucus content, whereas, the level/activities of catalase, superoxide dismutase, glutathione and malondialdehyde were also ameliorated after the administration of Triphala extract in experimental peptic ulcer disease model. In addition, the findings from our biochemical investigations are also well corroborated by histopathological observations. In conclusion, the current study demonstrates that swim-stress results in the development of gastric ulcers and damages the gastric mucosa along with the altered redox homeostasis in rats and Triphala extract exerts significant curative effects in posttreatment swim-stress-induced peptic ulcer disease rat model and may later be investigated and promoted for human clinical application

Berberis aristata and its secondary metabolites: Insights into nutraceutical and therapeutical applications

Considering the rising global health challenges and public expectations in terms of safety and cost effectiveness, it is necessary to promote effective, safer and cheaper alternative treatment options, particularly to benefit low- and middle-income countries (LMICs). Therapeutic regimens implying natural sources i.e., plants and their secondary metabolites have been trusted by a large proportion of sufferers and extensively searched for their pharmacological actions. Berberis aristata, commonly known as Zarishk, Daruharidra and Indian barberry, is being used in traditional medicine systems across the globe, particularly Asian countries i.e., India and China, and has also gained much attention in the current era of modern medicine. The protective effects of B. aristata against a number of diseases are attributed to its bioactive metabolites, mostly alkaloids, including berberine, berbamine, aromoline, jatrorrhizine, oxyberberine, palmatine, tetrahydropalmatine, and lupeol. However, a comprehensive report describing the ethnopharmacological relevance, important secondary metabolites, cytotoxicity, and recent advances in its therapeutic efficacy against various ailments is either outdated or still lacking. Therefore, the current review summarizes the recent updates regarding the implications of B. aristata and its potential bioactive secondary metabolites in targeting various acute and chronic diseases including diabetes, cardiovascular complications, cancer, hepatic dysfunction, infectious diseases, oxidative stress, inflammation, neurodegeneration, and ageing-associated symptoms with special emphasis on the biochemical and molecular mechanisms/pathways

Target-Based Virtual and Biochemical Screening Against HMG-CoA Reductase Reveals Allium sativum-Derived Organosulfur Compound N-Acetyl Cysteine as a Cardioprotective Agent

In the present study, we evaluate garlic, Allium sativum L., Amaryllidaceae, derived natural organosulfur compounds as effective antioxidant as well as inhibitors of human β-hydroxy-β-methyl-glutaryl-CoA reductase. The initial in silico screening analysis of organosulfur compounds depicted that among all the tested products, N-acetylcysteine, S-ethyl-L-cysteine, alliin, and S-allyl-L-cysteine were among the best commercially available modulators of HMG-R activity (ΔG: − 4.59, − 4.57, − 4.56, and − 4.53 kcal/mol, respectively), when compared to pravastatin (ΔG: − 4.80 kcal/mol). The above-mentioned organosulfur compounds also exhibited an intense DPPH and ABTS radical scavenging potential with the best IC50 observed in N-acetylcysteine, i.e., 7.031 ± 0.51 μM and 5.77 ± 0.22 μM, respectively, which was much better than the IC50 value of ascorbic acid (16.25 ± 0.62 μM and 26.73 ± 0.53 μM, respectively). On the other hand, N-acetylcysteine, S-ethyl-L-cysteine, and alliin exhibited significant in vitro HMG-R inhibitory activity with IC50 of 139.26 ± 1.8 μM, 264.66 ± 5.8 μM, and 292.86 ± 6.8 μM, respectively. Additionally, our enzyme kinetics studies revealed that N-acetylcysteine exhibits competitive inhibition against in vitro β-hydroxy-β-methyl-glutaryl-CoA reductase activity. Based in our in silico and in vitro studies, we concluded that among other selected organosulfur compounds, N-acetylcysteine possesses significant antioxidant potential and competitively inhibits the enzymatic activity of β-hydroxy-β-methyl-glutaryl-CoA

Targeting SARS-CoV-2 main protease (Mpro) and human ACE-2: A virtual screening of carotenoids and polyphenols from tomato (Solanum lycopersicum L.) to combat Covid-19

Background Human angiotensin-converting enzyme-2 (ACE-2) and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) main protease (Mpro) have been established as the prime targets to restrict viral invasion and replication inside the host, respectively. Methods The current study delineated the SARS-CoV-2 Mpro as well as human ACE-2 inhibitory potential of carotenoids and polyphenols from tomato (Solanum lycopersicum L.) via in-silico interaction studies. Results Our drug-likeness studies showed that the selected carotenoids and polyphenols exhibited acceptable Lipinski’s score and ADME determinants. Further, in-silico molecular modelling studies revealed that β-carotene, among other carotenoids, topped the binding score (ΔG: −6.75 kcal/mol; Ki: 11.32 μM) against SARS-CoV-2 Mpro, whereas, cyanidin was the best inhibitor of SARS-CoV-2 Mpro (−7.24 kcal/mol; Ki: 4.92 μM) amongst polyphenols. Similarly, α-carotene from carotenoids exhibited strongest human ACE-2 inhibitory activity (ΔG: −8.85 kcal/mol; Ki: 326.13 μM), whereas, cyanidin from polyphenols showed best binding affinity against human ACE-2 (ΔG: −7.24 kcal/mol; Ki: 4.89 μM). In contrast, 6-(ethylamino)-pyridine-3-carbonitrile, standard inhibitor of SARS-CoV-2 Mpro, exhibited comparatively weaker binding (ΔG: −4.78 kcal/mol; Ki: 267.49 μM), whereas, telmisartan (reference ACE-2 inhibitor) also exhibited lesser affinity (ΔG: −6.40 kcal/mol; Ki: 20.40 μM). Further exploration via MDS studies also validated the dynamic behavior and stability of protein-ligand complexes as evident by desirable RMSD, RMSF, Rg, and SASA. Conclusion The current study established carotenoids and polyphenols from S. lycopersicum L. as finer substitutes of reference standards against SARS-CoV-2 Mpro and human ACE-2 activity in combating SARS-CoV-2 infection

Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: <i>in vitro</i> and <i>in silico</i> study

<p>This study initially aimed to depict the molecular rationale evolving the role of lycopene in inhibiting the enzymatic activity of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase via <i>in vitro</i> and <i>in silico</i> analysis. Our results illustrated that lycopene exhibited strong HMG-CoA reductase inhibitory activity (IC₅₀ value of 36 ng/ml) quite better than pravastatin (IC₅₀ = 42 ng/ml) and strong DPPH free radical scavenging activity (IC₅₀ value = 4.57 ± 0.23 μg/ml) as compared to ascorbic acid (IC₅₀ value = 9.82 ± 0.42 μg/ml). Moreover, the <i>K</i>_<i>i</i> value of lycopene (36 ng/ml) depicted via Dixon plot was well concurred with an IC₅₀ value of 36 ± 1.8 ng/ml. Moreover, molecular informatics study showed that lycopene exhibited binding energy of −5.62 kcal/mol indicating high affinity for HMG-CoA reductase than HMG-CoA (Δ<i>G</i>: −5.34 kcal/mol). Thus, <i>in silico</i> data clearly demonstrate and support the <i>in vitro</i> results that lycopene competitively inhibit HMG-CoA reductase activity by binding at the hydrophobic portion of HMG-CoA reductase.</p

Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential

A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screened for their anticancer activity. Our molecular docking analysis revealed that among all derivatives of SOXs (4a–4h), 4a has a substantial binding affinity (∆G) −6.65, −6.55, −8.73, and −7.27 Kcal/mol with CD-44, EGFR, AKR1D1, and HER-2, respectively. A functional study demonstrated that SOX 4a has a substantial impact on human cancer cell phenotypes exhibiting abnormality in cytoplasmic and nuclear architecture as well as granule formation leading to cell death. SOX 4a treatment robustly induced reactive oxygen species (ROS) generation in cancer cells as observed by enhanced DCFH-DA signals. Overall, our results suggest that SOX (4a) targets CD-44, EGFR, AKR1D1, and HER-2 and induces ROS generation in cancer cells. We conclude that SOX (4a) could be explored as a potential chemotherapeutic molecule against various cancers in appropriate pre-clinical in vitro and in vivo model systems

Assessment of the mechanical and durability characteristics of bio-mineralized Bacillus subtilis self-healing concrete blended with hydrated lime and brick powder

Cement is the main constituent of the concrete structure. Using rejected brick as pozzolana in replacement of cement reduced the utilization of natural resources, conserved the environment, and controlled waste disposal. Hydrated lime has been utilized as a chemical additive to improve the pozzolanic reaction of finely ground waste brick particles. This research investigates the process of biomineralization to enhance the strength and durability characteristics of bacterial concrete incorporating hydrated lime and brick powder (HBr). In this context, cement was partially replaced with HBr in different proportions 10%, 20%, and 30% by weight. Furthermore, the HBr mixtures were meticulously prepared with and without the incorporation of Bacillus subtilis. Tests for strength and durability were performed at the age of 28 and 56 days of concrete. The self-healing proficiency of the bacterial concrete was evaluated through compressive strength, water permeability, and chloride penetration, while the microstructure analysis was conducted using field emission scanning electron microscopy (FESEM) and energy dispersive spectroscopy (EDS). The results show that at the age of 56 days, CaCO3 precipitation caused by Bacillus subtilis increases the compressive strength of BHBr10 by 19.07%. The durability properties in terms of chloride ion penetrability and water permeability exhibited substantial improvements of 40.03% and 61.9% respectively. Additionally, the FESEM micrographs along with the EDS analysis corroborated the presence of CaCO3 precipitation crystals