Synergistic inhibitory actions of resveratrol, epigallocatechin-3-gallate, and diallyl trisulfide against skin cancer cell line A431 through mitochondrial caspase dependent pathway: a combinational drug approach.

The harmful effect of chemotherapeutic side effects has paid a way to discover a novel with curative way for skin cancer treatment. Skin cancer prevention is more viable with the use of combination of bioactive agents than using of single bioactive compounds. Present work was demonstrated to evaluate the interaction of Resveratrol (Res), Epigallocatechin-3-gallate (EGCG), and diallyl trisulfide (DATS) with each other as a binary combination on A431 cells. Nuclear fragmentation analysis of combination of bioactive agents using DAPI analysis, detection of apoptosis, analysis of cell cycle, ROS assay, antimigration assays, and western blotting were implemented to study the combination of bioactive compounds on A431 cell line. Among the selected combination EGCG + DATS had a synergetic effect reducing cellular migration, increased intercellular reactive oxygen species generation, condensation, cell phagocytosis induced by phosphatidylserine externalization, rise in sub-G1 DNA content, and S-phase were cell cycle arrest. The combinations EGCG + DATS induced apoptotic proteins in A431 cells by upregulation of proapoptotic Bax and Bad proteins, a downmodulation of anti-apoptotic proteins Bcl2 and caspases (caspase-3, and -9) activity got triggered by intrinsic pathway. The combination of EGCG + DATS showed good anticancer potential against A431 skin cancer cell line via the mitochondrial caspase dependent pathway with very strong synergism. This finding will help to produce a novel combination/chemoprevention using dietary bioactive agents (EGCG + DATS) for the treatment of skin cancer after clinical trial.

Insights for integrative medicinal potentials of Ethiopian Kale (Brassica carinata): Investigation of antibacterial, antioxidant potential and phytocompounds composition of its leaves.

Objective: To compare the phytochemical and antimicrobial activity of Ethiopian Kale leaves infusions, investigate the antioxidant activity and profile the major phytochemicals existing in the better solvent system. Methods: Ethiopian Kale leaves were collected from Addis Ababa, Ethiopia, and extracted using different solvents. The qualitative phytochemical analysis, antibacterial assays, and Fourier Transform Infrared (FTIR) analysis are executed for all extracts. Antioxidant assay and Gas Chromatography-Mass Spectrometry (GC-MS) analysis are carried out for the solvent system, which showed better activity in preliminary studies. Results: The qualitative phytochemical analysis exposed the presence of different classes of phytoconstituents in most of the tested extracts. The broad spectrum of antibacterial activity (7-15 mm) was noted against the tested bacterial species. The functional groups of the extracts are reported by FTIR analysis. The antioxidant ability of ethanol extract was found to be (62.92 ± 0.34)% for 2,2-diphenyl-1-picrylhydrazyl (DPPH*) assay and (71.12 ± 0.41)% for 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. More than 17 major phytocompounds in ethanol extract were profiled by GC-MS analysis. Conclusion: The ethanol extract of Ethiopian Kale leaves contain a good source of phytochemicals and it can be a significant source for various functional applications.

Biochemical fingerprint and pharmacological applications of Barleria noctiflora L.f. leaves.

Background Antioxidant and antihistamine agents from Barleria noctiflora L.f. as natural source due to the existing modern medicine give various adverse effects to overcome these problems with natural products. MethodsB. noctiflora leaves extract was fractionated with column chromatography; the homogenized fractions were monitored with thin layer chromatography (TLC) and characterized by using UV-visible, FT-IR, 1H NMR, 13C NMR and mass spectrometry spectral studies. The volatile phytoconstituents of B. noctiflora extract were analysed by gas chromatography-mass spectrometry. Phytoconstituents from B. noctiflora leaves extract were screened for their antioxidant and antihistamine potential in vitro (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid radical decolouration assay, nitric oxide radical scavenging activity, superoxide radical scavenging activity and hydrogen peroxide radical scavenging activity) and in silico (molecular docking), respectively. Results Antioxidant and antihistamine barlerinoside has been isolated and characterized from the leaves of B. noctiflora L.f. Barlerinoside revealed their free-radical scavenging ability on OH-, OH•, NO-, O2- and H2O2 radicals and found high percentage inhibition against OH- radical at the IC50 value of 50.45±2.52  µg. The methanol (MeOH) extract of B. noctiflora leaves contains cyclotene; N,N-dimethylglycine; tetrahydrocyclopenta [1,3] dioxin-4-one; phenol, 2-methoxy-; benzofuran, 2-methyl-; 1,4:3,6-dianhydro-α-d-glucopyranose; 2-methoxy-4-vinylphenol; 1,3;2,5-dimethylene-l-rhamnitol; levoglucosan and bicyclo[2.2.2]oct-7-ene-2,5-dione as being the major compounds. Among phytoconstituents present in the extract, the hexestrol; 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester; 1-(3,6,6-trimethyl-1,6,7,7a-tetrahydrocyclopenta[c]pyran-1-yl) ethanone; megastigmatrienone; furan interacted with histamine H1 receptor and bind at GLU-177 and ASP-178 with high binding energy score -13.95, -13.41, -12.56, -12.03, and -11.72 kcal/mol, respectively, and the expected hydrolysed products of compound-1a and compound-1b from barlerinoside showed -8.91 and -8.68 kcal/mol binding energy against the histamine H1 receptor. This showed that the active ligands exactly bind with active binding site of the protein. ConclusionsWe can conclude that isolated barlerinoside from B. noctflora L.f. has potent antioxidant activity against synthetic free radicals and antihistamine activity against histamine H1 receptor.

Antihistamine from Tragia involucrata L. leaves.

BACKGROUND: Synthetic antihistamine drugs cause various adverse effects to overcome these problems with natural phytomedicine or phytoconstituents. METHODS: Tragia involucrata leaves were extracted with soxhlet apparatus and fractionated with column chromatography the homogenized fractions were monitored with thin layer chromatography (TLC) and characterized by using UV-visible, FT-IR, 1H NMR, 13C NMR and MS spectral studies. Isolated compounds were screened their antihistamine activity on ileum preparation, bronchoconstriction and triple response on histamine-induced guinea pig. RESULTS: Antihistamine 5-hydroxy-1-methylpiperidin-2-one has been isolated and characterized from the leaves of Tragia involucrata L. A promising muscle relaxant, bronchorelaxant and anti-allergic effect of 5-hydroxy-1-methylpiperidin-2-one was observed in histamine-induced guinea pig and found to be 55.54±2.78% protection at the dose level of 12.5 mg/kg in bronchoconstriction effect and 49.05±2.45% protection in triple response. These findings were confirmed by in silico molecular docking also against histamine H1 receptor compared with chlorpheniramine maleate and mepyramine. This shows that the 5-hydroxy-1-methylpiperidine-2-one possess good inhibitory effect on histamine-induced guinea pig. The muscle relaxant, bronchodilating and anti-allergic potency of 5-hydroxy-1-methylpiperidin-2-one has been discussed in context with its probable profile as an anti-asthmatic agent from T. involucrata L. leaves. CONCLUSIONS: We can conclude that isolated 5-hydroxy-1-methylpiperidin-2-one from T. involucrata L. has potent antihistamine agent on histamine-induced guinea pig.