TCQA, A Natural Caffeoylquinic Acid Derivative Attenuates H2O2-Induced Neuronal Apoptosis by Suppressing Phosphorylation of MAPKs Signaling Pathway

Abstract1,3,5-Tri-O-caffeoyl quinic acid is a caffeoylquinic acid derivative isolated from the roots of Arctium lappa L. Our previous studies have revealed that the ethyl acetate extract of the roots of A. lappa L. and the caffeoylquinic acids contained in it possess antioxidant properties, especially 1,3,5-tri-O-caffeoyl quinic acid. The present study aimed to investigate the protective effects of 1,3,5-tri-O-caffeoyl quinic acid against hydrogen peroxide-induced oxidative stress and explore the underlying mechanism. We found that 1,3,5-tri-O-caffeoyl quinic acid prevented the decline of cell viability and excessive release of lactate dehydrogenase induced by hydrogen peroxide. In addition, Hoechst 33 342 staining and Annexin V-PI double staining showed that 1,3,5-tri-O-caffeoyl quinic acid inhibited hydrogen peroxide-induced neuronal cell apoptosis. 1,3,5-Tri-O-caffeoyl quinic acid reduced the excessive production of intracellular reactive oxygen species, decreased the malondialdehyde content, and improved the activity of superoxide dismutase. Furthermore, 1,3,5-tri-O-caffeoyl quinic acid restored the loss of mitochondrial membrane potential in SH-SY5Y cells induced by hydrogen peroxide. 1,3,5-Tri-O-caffeoyl quinic acid downregulated the overexpression of proapoptotic proteins, including Bax, cytochrome c, cleaved caspase-9, and cleaved caspase-3 as well as promoted the expression of the antiapoptotic protein Bcl-2. Moreover, the phosphorylation of mitogen-activated protein kinases induced by hydrogen peroxide was inhibited by 1,3,5-tri-O-caffeoyl quinic acid. Pretreatment with 1,3,5-tri-O-caffeoyl quinic acid also promoted the activation of phosphorylated Akt. Taken together, these findings suggest that 1,3,5-tri-O-caffeoyl quinic acid exerts protective effects against hydrogen peroxide-induced neuronal apoptosis. In addition, inhibition of the mitogen-activated protein kinase signaling pathway and the activation of Akt are implicated in the antioxidant activity of 1,3,5-tri-O-caffeoyl quinic acid, giving new insight in searching for a compound with antioxidant activity for the treatment of oxidative stress-associated neurological diseases.

Phytochemicals from Rhizophora mucronata Propagules, Its In Vitro Anti-Cancer and In Silico Drug-Likeness Potential

This is the first report to identify the presence of 3-O-caffeoyl quinic acid (1), 4-O-caffeoyl quinic acid (2), 5-O-caffeoyl quinic acid (3), epi-catechin (4), and procyanidin B2 (5) in the young propagules of Rhizophora mucronata. Compounds 2–5 were purified and then treated against breast, colorectal, and ovarian cancer cell lines for 72 h and the results of the Sulphorhodomine-B (SRB) assay were evaluated for percent cell viability and IC50 values. Epi-catechin, 4-O-caffeoyl quinic acid, 5-O-caffeoyl quinic acid and procyanidin B2 showed strong to moderate inhibitory effects when treated on breast (T47D), colorectal (HT29), and ovarian (A2780, SKOV3) cancer cell lines with IC50 values ranging from 16.77 ± 0.58 to 28.28 ± 0.89 μg/mL. In silico evaluation was performed to evaluate the drug-likeness and toxicological effects of these compounds using Molinspiration calculation and OSIRIS program. It was found that compounds 2, 3, and 4 have the potential to be orally active and have a low risk in exerting the mutagenic, tumorigenic, irritant, and reproductive effects.

Phytochemical Profiling of Methanolic Fruit Extract of Gardenia latifolia Ait. by LC-MS/MS Analysis and Evaluation of Its Antioxidant and Antimicrobial Activity

Gardenia latifolia Ait. (Rubiaceae) is also known as Indian Boxwood is a small deciduous tree often growing in southern states of India. In the present study, phytochemical profiling of methanolic extract of G. latifolia fruits were carried out using FTIR and LC-MS/MS analysis. Besides, its antioxidant and antimicrobial potential have been analysed using DPPH activity, differential pulse voltammetry and resazurin microtiter assay, respectively. Phytochemical profiling revealed the presence of 22 major diversified compounds and main were 3-caffeoyl quinic acid (chlorogenic acid), 3,4-Di-O-caffeoyl quinic acid, 6-O-trans-feruloylgenipin gentiobioside, 10-(6-O-trans sinapoyl glucopyranosyl) gardendiol, isoquercitrin, scortechinones, secaubryenol, iridoids and quercetin 3-rutinoside (rutin). The extract showed antioxidant activity (IC50 = 65.82) and powerful antibacterial activity with lowest minimum inhibitory concentration against Gram-positive Staphylococcus aureus (15.62 µg/µL), Bacillus subtilis (31.25 µg/µL) than gram negative Escherichia coli (62.5 µg/µL), Klebsiella pneumoniae (62.5 µg/µL), Pseudomonas aeruginosa (31.25 µg/µL). This study shows that the fruits of G. latifolia have tremendous potential to be used in food industries, phyto-therapeutics and cosmetic industries.

Aronia melanocarpa Fruit and Leaves Hot-Assisted Ethanolic Extracts Antioxidant Activity

Aronia melanocarpa L. fruit (common black chokeberry) is one of the most abundant sources of antioxidant compounds in the plant world, superior to all edible fruits; chokeberry fruits contain up to 100 g total phenols per kg fresh material, predominantly (−)epicatechin, cyanidin-3-glycosides and procyanidins (60%), added to quercetin and caffeoyl quinic acid derivates.

Hydroxycinnamic Acids and Carotenoids of Dried Loquat Fruit cv. ‘Algar’ Affected by Freeze-, Convective-, Vacuum-Microwave- and Combined-Drying Methods

The effect of different drying techniques (freeze, convective, vacuum-microwave and combined drying) on the drying kinetics, the phytochemical compounds and sensory characteristics in loquat cultivar ‘Algar’ was studied. The convective drying resulted in the highest amount of total hydroxycinnamic acids (5077 mg/kg wet weight (ww)), with 3-caffeoyl quinic acid and 5-caffeoyl quinic acid being the greatest carotenoids. The highest values of total carotenoids were obtained by the freeze-drying technique (2601 mg/kg ww), followed by all convective treatments and vacuum-microwave at 360 W. The highest carotenoid was β-carotene. The ABTS+• (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric Ion Reducing Antioxidant Power) values ranged from 2.04 up to 3.27 mmol Trolox/100 g ww, and from 1.89 up to 2.29 mmol Trolox/100 g ww, respectively. As expected, the color difference of freeze-dried samples was the lowest (7.06), similar to combined drying conditions (9.63), whilst the highest value was found after convective drying (37.0). All treatments were sensory acceptable (no off-flavors). However, still, further research is needed to fully optimize these studied drying treatments because the freeze-dried sample still had higher carotenoid content and better instrumental color parameters. Although recently the impact of microwave drying has been studied, this is the first work comparing phytochemical composition of loquat fruit under the different drying methods mentioned above.

Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi

The phytochemical investigation on the roots of Acanthopanax henryi (Araliaceae) resulted in the discovery of twenty compounds whose chemical structures were elucidated by the analysis of 1D-, 2D-NMR, mass spectrometry data, other physicochemical properties, and a comparison of the spectral data with the literature. They were identified as (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), 6-methoxy-7-hydroxycoumarin (5), behenic acid (6), 3-O-caffeoyl-quinic acid (7), 5-O-caffeoyl-quinic acid (8), 1,3-di-O-caffeoyl-quinic acid (9), 1,4-di-O-caffeoyl-quinic acid (10), 1,5-di-O-caffeoyl-quinic acid (11), (+)-threo-(7R,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (12), (+)-erythro-(7S,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (13), ferulic acid (14), caffeic acid (15), stigmasterol (16), β-sitosterol (17), adenosine (18), syringin (19), and trans-coniferin (20). Among these isolates, compound 3 showed inhibitory activity against lipopolysaccharide- (LPS-) induced nitric oxide (NO) and prostaglandin E2 (PGE2) production with IC50 values of 2.22 ± 0.11 and 2.28 ± 0.23 μM, respectively. The effects of compound 3 were associated with the suppression of LPS-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Furthermore, compound 3 negatively regulated the production of interleukin- (IL-) 1β and tumor-necrosis factor- (TNF-) α at the transcriptional level in LPS-stimulated BV2 microglial cells. These antineuroinflammatory effects of compound 3 were mediated by p38 mitogen-activated protein kinase (MAPK).