Isolation and Antibacterial Properties of Phenyl Acrylic Acid Derivatives from Balanophora elongata Blume

Balanophora elongata (Balanophoraceae) is a tropical parasitic flowering plant 9 cm in height. Four known phenyl acrylic acid derivatives, methyl caffeate (1), caffeic acid (2), 1,6-di-O-caffeoyl-β-D-glucopyranose (3), and coniferin (4), were isolated from this plant. Structural elucidation of the isolated compounds was determined by IR, LC-ESI-MS, 1D and 2D NMR. Extracts and isolated compounds were tested toward some standard human pathogenic bacteria using the agar disk diffusion method. Their inhibition zones were compared to that of chloramphenicol as positive control. Compound 1 showed inhibition toward Streptococcus mutans, while compound 3 and 4 inhibited Staphylococcus aureus.

Phytochemical Characterization and Antioxidant Bioactivity of Andrographis paniculata (Nees)

Background: Medicinal plants are natural sources of antioxidants effective in the treatment of radical mediated diseases. This study evaluated the in-vitro antioxidant and phytochemical constituents of the methanolic leaves extract of Andrographis paniculata . Methods: Fresh A. paniculata leaves were harvested from a local far m, air -dried and extracted with methanol. Chemical composition, antioxidant activities, and α-amylase enzyme inhibitory potentials of the extract were determined Results: The extract of A. paniculata concentration-dependently scavenges 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2’azinobis (3-ethylbenzothiazoline-6-sulphonic acids) (ABTS) radicals. It scavenges nitric oxide radicals with IC50 of 145.99 μg/ml compared to 167.17 μg/ml of standard ascorbic acid and has 41% activity of standard ascorbic acid ferric reducing power. The extract also inhibited the induction of lipid peroxidation and α-Amylase activity in a concentration-dependent manner. The phytochemical assays employed revealed the presence of various phytochemicals in the extract. Further analysis with gas-chromatography revealed the possible presence of Andrographolide, Deoxyandrographolide, Apigenin, Kaempferol, Quercetin, Methyl vanillate, Methyl Caffeate, Beta-sitosterol, Vanillic acid in the extract. The total phenolics content was found to be 29.11mg GAE/g, and proximate analysis revealed the moisture content, crude protein, crude fat, crude fiber, total ash, and Nitrogen free extract to be 21.89%, 5.66%, 8.74%, 0.95%, 6.87%, and 55.89% respectively. Conclusion: The plant A. paniculata demonstrated good antioxidant potentials and contain various phytochemicals. Therefore, it could be inferred that the effectiveness of A. paniculata as a medicinal plant could be due to the presence of various phenolics and antioxidant compounds in the plant.

Compounds Isolated from the Ethyl Acetate Fraction of Canna edulis Ker Gawl Rhizomes

Three compounds were isolated from the rhizome part of Canna edulis for the first time including liquiritigenin, methyl caffeate and uracil. Their structures were elucidated by spectroscopic methods as MS and NMR. Keywords Canna edulis Ker Gawl, liquiritigenin, methyl caffeate, uracil. References [1] T. H. Vu, Q. U. Le, Edible Canna (Canna edulis Ker), A Potential Crop for Vietnam Food Industry, International Journal of Botany Studies, Vol. 4, No. 4, 2019, pp. 58–59.[2] N. Tanakar, The Utilization of Edible Canna Plants in Southeastern Asia and Southern China, Economic Botany, Vol. 58, No. 1, 2004, 112–114.[3] A. S. A. Snafi, Bioactive Components and Pharmacological Effects of Canna indica - an Overview, International Journal of Pharmacology and Toxicology, Vol. 5, No. 2, 2015, pp. 71–75.[4] X. J. Zhang, Z. W. Wang, Q. Mi, Phenolic Compounds from Canna edulis Ker Residue and Their Antioxidant Activity, LWT - Food Science Technology, Vol. 44, No. 10, 2011, pp. 2091–2096, https://doi.org/10.1016/j.lwt.2011.05.021. [5] F. Xie, S. Gong, W. Zhang, J. Wu, Z. Wang, Potential of Lignin from Canna edulis Ker Residue in The Inhibition of α-d-glucosidase: Kinetics and Interaction Mechanism Merging with Docking Simulation, International Journal of Biology and Macromolecules, Vol. 95, 2017, pp. 592–602, https://doi.org/10.1016/j.ijbiomac.2016.11.100.[6] J. Zhang, Z. W. Wang, Soluble Dietary Fiber from Canna edulis Ker By-product and Its Physicochemical Properties, Carbohydrates Polymers, Vol. 92, No. 1, 2013, pp. 289–296, http:/doi.org/10.1016/j.carbpol.2012.09.067.[7] T. M. H. Nguyen, H. L. Le, T. T. Ha, B. H. Bui, N. T. Le, V. H. Nguyen, T. V. A. Nguyen, Inhibitory Effect on Human Platelet Aggregation and Coagulation and Antioxidant Activity of Canna edulis Ker Gawl Rhizhomes and Its Secondary Metabolites, Journal of Ethnopharmacology, Vol. 263, 2020, pp. 113-136, https:/doi.org/10.1016/j.jep.2020.113136.[8] T. A. Y. Diaa, M. A. Ramada, A. A. Khalifa, Acetophenones, a Chalcone, a Chromone and Flavonoids from Pancratium Maritimum, Phytochemistry, Vol. 49, No. 8, pp. 1998, pp. 2579-2583, http:/doi.org/10.1016/S003109422(98)00429-4. [9] W. Koji, Y. Osanai, T. Imaizumi, S. Kanno, M. Takeshita, M. Ishikawa, Inhibitory Effect of The Alkyl Side Chain of Caffeic Acid Analogues on Lipopolysaccharide-induced Nitric Oxide Production in RAW264.7 Macrophages, Bioorganic Med. Chem., Vol. 16, No. 16, 2008, pp. 7795–7803, https:/doi.org/10.1016/j.bmc.2008.07.006.[10] C. Y. Wang, L. Han, K. Kang, C. L. Shao, Y. X. Wei, C. J. Zheng, H. S Guan, Secondary Metabolites From Green Algae Ulva Pertusa, Chemistry of Natural Compounds Vol. 46, No. 5, 2010, pp. 828-830.[11] C. T. Inh, N. T. H. Van, P. M. Quan, T. T. Q. Trang, T. A. Vien, N. T. Thuy, D. T. Thao, New Diterpenoid Isolated from Medicinal Plant Euphorbia tithymaloides (P.), Vietnam J. Chem., Vol. 54, 2016, pp. 274-279, https:/doi.org/10.15625/0866-7144.2016-00304 (in Vietnamese).[12] Q. Y. Li, H. Liang, B. Wang, Z. Z. Zhao, Chemical Constituents of Momordica charantia L, Yao Xue Xue Bao, Vol. 44, No. 9, 2009, pp. 1014-1018.[13] V. T. Diep, L. T. Loan, N. T. Thu, T. T. Ha, N. M. Khoi, N. H. Tuan, D. T. Ha, Triterpen, Flavonoid and Pyrimidine Compounds from The Aerial Parts of Dregea volubilis, Journal of Medicinal Materials, Vol. 24, No. 6, 2019, pp. 329-332.[14] H. M. Eid, D. Vallerand, A. Muhammad, T. Durst, P. S. Haddad, L. C. Martineau, Structural Constraints and the Importance of Lipophilicity for the Mitochondrial Uncoupling Activity of Naturally Occurring Caffeic Acid Esters with Potential for the Treatment of Insulin Resistance, Biochemical Pharmacology, Vol. 79, No. 3, 2010, pp. 444–454, https:/doi.org/10.1016/j.bcp.2009.08.026.[15] K. Takahashi, Y. Yoshioka, E. Kato, S. Katsuki, O. Iida, K. Hosokawa, J. Kawabata, Methyl Caffeate as a Glucosidase Inhibitor from Solanum Torvum fruits and the Activity of Related Compounds, Bioscience, Biotechnology and Biochemistry, Vol. 74, No. 4, 2010, pp. 741–745, https:/doi.org/10.1271/bbb.9087.[16] S. M. Fiuza, C. Gomes, L. J. Teixeira, M. T. G. D. Cruz, M. N. Cordeiro, N. Milhazes, F. Borges, M. P. Marques, Phenolic Acid Derivatives with Potential Anticancer Properties, a Structure-Activity Relationship Study Part 1: Methyl, Propyl and Octyl Esters of Caffeic and Gallic Acids, Bioorgan Med Chem, Vol. 12, No. 13, 2004, pp. 3581-3589, https:/doi.org/10.1016/j.bmc.2004.04.026.[17] S. P. Lee, G. Jun, E. Yoon, S. Park, C. Yang, Inhibitory Effect of Methyl Caffeate on Fos-Jun-DNA Complex Formation and Suppression of Cancer Cell Growth, Bulletin of Korean Chemical Society, Vol. 22, No. 10, 2001, pp. 1131-1135.

Novel Poly-(Lactic-Co-Glycolic Acid) Targeted Nanoparticles Conjunct with Antibody for the Enhancement of Antibacterial Activity against Ralstonia solanacearum

Due to the strong pathogenicity of Ralstonia solanacearum, a variety of strategies have been used to develop antibacterial agents; however, antibacterial drugs with targeted effects on R. solanacearum remain lacking. Herein, we present a nanoagent targeting R. solanacearum based on our previous research on poly-(lactic-co-glycolic acid) (PLGA) particles (PLGA-NPs) loaded with methyl caffeate and caffeic acid phenethyl ester. Antibodies that have specific effects on R. solanacearum, which were verified using immuno-PCR, were first used to prepare PLGA-targeted nanoparticles (PLGA-TNPs). The antibody coupling process was investigated in terms of antibody binding degree and antibacterial activity. The EC50 value of PLGA-TNPs was 0.021 mg/mL, which was significantly reduced by 92% in comparison to PLGA-NPs. PLGA-TNPs had a perforating effect on the cell membrane of R. solanacearum, but no effects on Escherichia coli according to the SEM results. In addition, a downregulation of the pathogenicity-related genes compared to PLGA-NP treatment was observed, and the expression of egl, phcA, phcB, pilT, polA-238, and pehC decreased by 78, 79, 87, 61, 58, and 41%, respectively. Therefore, PLGA-targeted nanoparticles not only enhance the activity against R. solanacearum, but also provide a new idea for controlling bacterial wilt.

Methyl Caffeate Isolated from the Flowers of Prunus persica (L.) Batsch Enhances Glucose-Stimulated Insulin Secretion

Phenolic compounds from natural products are considered effective enhancers of insulin secretion to prevent and treat type 2 diabetes (T2DM). The flowers of Prunus persica (L.) Batsch also contain many phenolic compounds. In this study, the extract of flowers of P. persica (PRPE) exhibited an insulin secretion effect in a glucose-stimulated insulin secretion (GSIS) assay, which led us to isolate and identify the bioactive compound(s) responsible for these effects. Compounds isolated from PRPE were screened for their efficacy in INS-1 rat pancreatic β-cells. Among them, caffeic acid (5), methyl caffeate (6), ferulic acid (7), chlorogenic acid (8), naringenin (11), nicotiflorin (12), and astragalin (13) isolated from PRPE increased GSIS without inducing cytotoxicity. Interestingly, the GSIS effect of methyl caffeate (6) as a phenolic compound was similar to gliclazide, an antidiabetic sulfonylurea drug. Western blot assay showed that methyl caffeate (6) enhanced the related signaling proteins of the activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), but also the phosphorylation of the total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, which influence β-cell function and insulin secretion. This study provides evidence that methyl caffeate (6) isolated from PRPE may aid in the management of T2DM.

AAPH or Peroxynitrite-Induced Biorelevant Oxidation of Methyl Caffeate Yields a Potent Antitumor Metabolite

Hydroxycinnamic acids represent a versatile group of dietary plant antioxidants. Oxidation of methyl-p-coumarate (pcm) and methyl caffeate (cm) was previously found to yield potent antitumor metabolites. Here, we report the formation of potentially bioactive products of pcm and cm oxidized with peroxynitrite (ONOO¯), a biologically relevant reactive nitrogen species (RNS), or with α,α′-azodiisobutyramidine dihydrochloride (AAPH) as a chemical model for reactive oxygen species (ROS). A continuous flow system was developed to achieve reproducible in situ ONOO¯ formation. Reaction mixtures were tested for their cytotoxic effect on HeLa, SiHa, MCF-7 and MDA-MB-231 cells. The reaction of pcm with ONOO¯ produced two fragments, an o-nitrophenol derivative, and a new chlorinated compound. Bioactivity-guided isolation from the reaction mixture of cm with AAPH produced two dimerization products, including a dihydrobenzofuran lignan that exerted strong antitumor activity in vitro, and has potent in vivo antimetastatic activity which was previously reported. This compound was also detected from the reaction between cm and ONOO¯. Our results demonstrate the ROS/RNS dependent formation of chemically stable metabolites, including a potent antitumor agent (5), from hydroxycinnamic acids. This suggests that diversity-oriented synthesis using ROS/RNS to obtain oxidized antioxidant metabolite mixtures may serve as a valid natural product-based drug discovery strategy.

Neuroprotective Effects of Methyl Caffeate against Hydrogen Peroxide-Induced Cell Damage: Involvement of Caspase 3 and Cathepsin D Inhibition

Finding effective neuroprotective strategies to combat various neurodegenerative disorders still remain a clinically unmet need. Methyl caffeate (MC), a naturally occurring ester of caffeic acid, possesses antioxidant and anti-inflammatory activities; however, its role in neuroprotection is less investigated. In order to better characterize neuroprotective properties of MC, we tested its effectiveness in various models of neuronal cell injury in human neuroblastoma SH-SY5Y cells and in mouse primary neuronal cell cultures. MC at micromolar concentrations attenuated neuronal cell damage induced by hydrogen peroxide (H2O2) in undifferentiated and neuronal differentiated SH-SY5Y cells as well as in primary cortical neurons. This effect was associated with inhibition of both caspase-3 and cathepsin D but without involvement of the PI3-K/Akt pathway. MC was neuroprotective when given before and during but not after the induction of cell damage by H2O2. Moreover, MC was protective against 6-OHDA-evoked neurotoxicity in neuronal differentiated SH-SY5Y cells via inhibition of necrotic and apoptotic processes. On the other hand, MC was ineffective in models of excitotoxicity (induced by glutamate or oxygen–glucose deprivation) and even moderately augmented cytotoxic effects of the classical apoptotic inducer, staurosporine. Finally, in undifferentiated neuroblastoma cells MC at higher concentrations (above 50 microM) induced cell death and when combined with the chemotherapeutic agent, doxorubicin, it increased the cell damaging effects of the latter compound. Thus, neuroprotective properties of MC appear to be limited to certain models of neurotoxicity and depend on its concentrations and time of administration.

Constituents of Xerolekia speciosissima (L.) Anderb. (Inuleae), and Anti-Inflammatory Activity of 7,10-Diisobutyryloxy-8,9-epoxythymyl Isobutyrate

Xerolekia speciosissima (L.) Anderb., a rare plant from the north of Italy, is a member of the Inuleae-Inulinae subtribe of the Asteraceae. Despite its close taxonomic relationship with many species possessing medicinal properties, the chemical composition of the plant has remained unknown until now. A hydroalcoholic extract from the aerial parts of X. speciosissima was analyzed by HPLC-DAD-MSn, revealing the presence of caffeic acid derivatives and flavonoids. In all, 19 compounds, including commonly found chlorogenic acids and less frequently occurring butyryl and methylbutyryl conjugates of dicaffeoylquinic and tricaffeoylhexaric acids, plus two flavonoids, were tentatively identified. Chromatographic separation of a hydroalcoholic extract from the capitula of the plant led to the isolation of (+)-dehydrodiconiferyl alcohol 4-O-β-glucopyranoside, quercimeritrin, astragalin, isoquercitrin, 6-hydroxykaempferol-7-O-β-glucoside, quercetagitrin, methyl caffeate, caffeic acid, protocatechuic acid, chlorogenic acid and 1,5-dicaffeoylquinic acid. Composition of a nonpolar extract from the aerial parts of the plant was analyzed by chromatographic methods supported with 1H-NMR spectroscopy. The analysis revealed the presence of loliolide, reynosin, samtamarine, 2,3-dihydroaromaticin, 2-deoxy-4-epi-pulchellin and thymol derivatives as terpenoid constituents of the plant. One of the latter compounds—7,10-diisobutyryloxy-8,9-epoxythymyl isobutyrate—at concentrations 0.5, 1.0 and 2.5 μM, significantly reduced IL-8, IL-1β and CCL2 excretion by LPS-stimulated human neutrophils.

Phenolic Compounds Isolated from Fruits of Cornus officinalis Sieb. et Zucc.

In this study, six phenolic compounds were isolated from the ethyl acetate of Cornus officinalis, including: Gallic acid (1), dimethyl malate (2), 1,4-dimethyl ester 2-(2-formyl-1H-pyrrol-1-yl)butanedioic acid (3), stageobester A (4), coroffester (5), and methyl caffeate (6). The structure of the compounds was determined by such spectroscopic methods as MS, NMR and by comparison with the published NMR data. This is the first time compounds 3-5 have been isolated from this species. Keywords Cornus officinalis, gallic acid, dimethyl malate, 1,4-dimethyl ester 2-(2-formyl-1H-pyrrol-1-yl)butanedioic acid, stageobester A, coroffester, methyl caffeate. References