Caffeoylmalic Acid

Antinociceptive Effect of Dillenia indica (Linn.) Mediated by Opioid and Cannabinoid Systems: Pharmacological and Chemical Studies.[Pubmed:38092696]

Chem Biodivers. 2024 Mar;21(3):e202301508.

Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D. indica have been used to treat general topical pain and inflammation, but with no scientific validation. Thus, aiming to study its chemical constitution and antinociceptive properties, the crude extract (CE) and fractions obtained from the fruits of D. indica were submitted to an in vivo pharmacological evaluation and a dereplication study by LC-MS/MS analysis, assisted by the Global Natural Product Social Molecular Networking (GNPS). The oral antinociceptive activity of the fruits of D. indica and the possible participation of the opioid and cannabinoid systems were demonstrated in the formalin-induced nociception model. The chemical dereplication study led us to identify several known chemical constituents, including flavonoids, such as Caffeoylmalic Acid, naringenin, quercetin, and kaempferol. According to literature data, our results are compatible with significant antinociceptive and anti-inflammatory activities. Therefore, the flavonoid constituents of the fruits of D. indica are probably responsible for its antioxidant, anti-inflammatory, and antinociceptive effects mediated by both opioid and cannabinoid systems, confirming its folk use in the treatment and relief of pain.

Protective Effect of Urtica dioica Extract against Oxidative Stress in Human Skin Fibroblasts.[Pubmed:38004322]

Life (Basel). 2023 Nov 9;13(11):2182.

Urtica dioica is a species with well-established significance in folk medicine in many countries. It was utilized to support the treatment of arthritis, allergies, and urinary tract disorders; however, the substantial presence of antioxidants suggests that nettle extract could also have a positive impact on the skin. The objective of this study was to assess the impact of nettle extract on human skin fibroblasts subjected to oxidative stress. Various solvents were tested to prepare an extract rich in polyphenolic compounds with high antioxidant potential. The chemical composition was determined using ultra-high-performance liquid chromatography with mass spectrometry (UPLC-DAD-MS). H(2)O(2) treatment was used to induce oxidative stress and cell viability, and the metabolism was evaluated through NR and MTT assays. Our study demonstrated that extraction with 80% ethanol, followed by the drying and re-dissolving of the extract in pure water, was more efficient than direct extraction with water. This yielded an extract rich in polyphenolic compounds, with chlorogenic acid and Caffeoylmalic Acid as the predominant compounds, averaging 64.9 and 114.4 microg/mL, respectively. The extract exhibited antioxidant properties in the DPPH and ABTS assays. Furthermore, it did not exhibit cytotoxicity and did not negatively affect cell metabolism. In addition, it effectively reduced ROS in the H(2)O(2)-stimulated cells, and at the highest concentration tested, the ROS levels returned to those of the untreated control. The extract also protected against H(2)O(2)-induced cytotoxicity. The cell viability was maintained at the level of the untreated control when the cells were pretreated with the extract before H(2)O(2) exposure. These findings indicate that U. dioica extract is a valuable and safe additive in skincare products.

Efficacy of Ficus carica leaf extract on morphological and molecular behavior of mice germ stem cells.[Pubmed:36060818]

Anim Reprod. 2022 Aug 19;19(2):e20220036.

Infertility is one of the most prevalent health disorders in reproductive-age males and females. Ficus carica (Fc), an herbal plant, has been used traditionally for the treatment of different diseases such as infertility especially in Iranian folk medicine. This study examined the effects of Fc leaf extract on the proliferation of mice spermatogonial stem cells (SSCs). Phenolic, flavonoid content, major polyphenolic compounds and antioxidant activity of the extract was evaluated respectively by Folin-Ciocateu, aluminum chloride, HPLC and the FRAP and DPPH methods. Testicular cells of neonate mice were extracted and their identity was confirmed using cytokeratin for Sertoli and Oct-4, CDHI and PLZF for SSCs. Effects of Fc (0.0875, 0.175, 0.35, 0.71 and 1.42 mg/ml) was evaluated at third, 7th, 9th and 14th days of culture by colony assay. The expression of the Mvh, GFRalpha1 and Oct-4 genes and the viability and proliferation of cultured cells was assessed at the end of the culture period. The extract has a rich phenolic and flavonoid content such as Rutin, Psoralen, Bergapten and Caffeoylmalic Acid using HPLC analysis. It also had a potent reducing and radical scavenging activity. Morphology of colonies was similar in all groups. Higher viability, proliferation, colony number and diameter of SSCs was seen in the presence of Fc leaf extract in a dose-dependent manner so that higher number and diameter of colonies were observed in two higher doses of 0.71 and 1.42 mg/ml, separately for each time point relative to other groups. The Mvh, Oct-4 and GFRalpha1 genes expression had no significant differences between groups. It seems that Fc leaf extract not only had no any cytotoxic effects on the viability and proliferation of SSCs but also support their stemness state. So, this culture system can be employed for enrichment of germ stem cells for use in clinical applications.

Comparative Metabolomic Profiling of Compatible and Incompatible Interactions Between Potato and Phytophthora infestans.[Pubmed:35464908]

Front Microbiol. 2022 Apr 8;13:857160.

Late blight is one of the main biological stresses limiting the potato yield; however, the biochemical mechanisms underlying the infection process of Phytophthora infestans remain unrevealed. In this study, the late blight-resistant potato cultivar Ziyun No.1 (R) and the susceptible cultivar Favorita (S) were inoculated with P. infestans. Untargeted metabolomics was used to study the changes of metabolites in the compatible and incompatible interactions of the two cultivars and the pathogen at 0, 48, and 96 h postinoculation (hpi). A total of 819 metabolites were identified, and the metabolic differences mainly emerged after 48 hpi. There were 198 and 115 differentially expressed metabolites (DEMs) in the compatible and incompatible interactions. These included 147 and 100 upregulated metabolites during the compatible and incompatible interactions, respectively. Among them, 73 metabolites were identified as the P. infestans-responsive DEMs. Furthermore, the comparisons between the two cultivars identified 57 resistance-related metabolites. Resistant potato cultivar had higher levels of salicylic acid and several upstream phenylpropanoid biosynthesis metabolites, triterpenoids, and hydroxycinnamic acids and their derivatives, such as sakuranetin, ferulic acid, ganoderic acid Mi, lucidenic acid D2, and Caffeoylmalic Acid. These metabolites play crucial roles in cell wall thickening and have antibacterial and antifungal activities. This study reports the time-course metabolomic responses of potatoes to P. infestans. The findings reveal the responses involved in the compatible and incompatible interactions of potatoes and P. infestans.

Phenolic Composition and alpha-Glucosidase Inhibition of Leaves from Chilean Bean Landraces.[Pubmed:35182308]

Plant Foods Hum Nutr. 2022 Mar;77(1):135-140.

The MeOH:H(2)O (7:3) extracts of leaves from Chilean bean landraces were assessed for total phenolic (TP), total flavonoid (TF), total proanthocyanidin (TPA) content, antioxidant capacity (ORAC, FRAP, TEAC, CUPRAC, DPPH) and the inhibition of enzymes associated with metabolic syndrome (alpha-glucosidase, alpha-amylase, pancreatic lipase). The chemical profiles were analyzed by HPLC-DAD. Higher antioxidant activity in the ORAC and CUPRAC assay was found for the landrace Coscorron, and the best effect in the TEAC for Sapito, respectively. The main phenolics were flavonol glycosides and caffeic acid derivatives. The extracts presented strong activity against alpha-glucosidase, but were inactive towards alpha-amylase and pancreatic lipase. The leaf extract from the Sapito landrace was fractionated to isolate the main alpha-glucosidase inhibitors, leading to Caffeoylmalic Acid with an IC(50) of 0.21 mug/mL. The HPLC fingerprints of the leaves differentiate three groups of chemical profiles, according to the main phenolic content. A significant correlation was found between the alpha-glucosidase inhibition, the content of Caffeoylmalic Acid (r = -0.979) and kaempferol 3-O-beta-D-glucoside (r = 0.942) in the extracts. The presence of alpha-glucosidase inhibitors in the leaves of Chilean beans support their potential as a source of bioactive compounds.

In-depth phytochemical and biological studies on potential AChE inhibitors in red and zigzag clover dry extracts using reversed-phase liquid chromatography (RP-LC) coupled with photodiode array (PDA) and electron spray ionization-quadrupole/time of flight-mass spectrometric (ESI-QToF/MS-MS) detection and thin-layer chromatography-bioautography.[Pubmed:34920306]

Food Chem. 2022 May 1;375:131846.

In the study, Trifolium medium L. and T. pratense L. were used to obtain lyophilisates which were named as TML and TPL, respectively. The former clover taxon represents a little explored species, while the latter one is often found in dietary supplements and functional foods due to the content of isoflavones that alleviate various menopausal symptoms. Detailed phytochemical profiles of both lyophilisates were examined and compared using coupled chromatographic (RP-LC) and spectroscopic PDA/ESI-QToF/MS-MS methods. A total of 54 and 55 compounds were identified in TML and TPL, respectively. Close chemotaxonomic similarities were confirmed for both clover taxa examined, especially in terms of the most abundant isoflavones and hydroxycinnamates. For the first time, neurotropic polyphenols (AChE inhibitors) were identified in clover extracts using TLC-bioautography. In this group, Caffeoylmalic Acid exhibited significant AChE inhibitory effect confirming the potential of TPL and TML to support physiological functions of the endocrine and nervous systems.

Prohydrojasmon Promotes the Accumulation of Phenolic Compounds in Red Leaf Lettuce.[Pubmed:34579452]

Plants (Basel). 2021 Sep 15;10(9):1920.

Prohydrojasmon (PDJ) is a synthetic jasmonate derivative that is primarily used as a growth regulator, but its mechanism of action is unclear. In this study, we elucidated the effects of PDJ on phytochemical production in red leaf lettuce. The PDJ treatments promoted the accumulation of phenolic compounds in aerial plant parts. An LC-MS analysis revealed that these accumulated compounds were identified as cyanidin-3-O-glucoside, cyanidin-3-O-(6''-O-malonyl)-glucoside and cyanidin-3-O-(6''-O-malonyl)-glucoside methyl ester. The abundance of these compounds in lettuce extracts increased significantly in response to the PDJ treatment. Additionally, the LC-MS analysis also identified the accumulated phenolic compounds in the extracts of PDJ-treated lettuce, including caffeoyltartaric acid, chlorogenic acid, Caffeoylmalic Acid, chicoric acid, and dicaffeoylquinic acid. Gene expression analyses indicated the PDJ treatments upregulated the expression of PAL, F3H, and ANS genes in lettuce. These results suggest that PDJ treatments enhance the expression of genes involved in the synthesis of anthocyanins and phenolic compounds, resulting in an increase in the quantities of these compounds, which reportedly have various functions affecting human physiology.

Simultaneous Determination of 78 Compounds of Rhodiola rosea Extract by Supercritical CO(2)-Extraction and HPLC-ESI-MS/MS Spectrometry.[Pubmed:34306755]

Biochem Res Int. 2021 Jul 6;2021:9957490.

The plant Rhodiola rosea L. of family Crassulaceae was extracted using the supercritical CO(2)-extraction method. Several experimental conditions were investigated in the pressure range of 200-500 bar, with the used volume of cosolvent ethanol in the amount of 1% in the liquid phase at a temperature in the range of 31-70 degrees C. The most effective extraction conditions are pressure 350 bar and temperature 60 degrees C. The extracts were analyzed by HPLC with MS/MS identification. 78 target analytes were isolated from Rhodiola rosea (Russia) using a series of column chromatography and mass spectrometry experiments. The results of the analysis showed a spectrum of the main active ingredients Rh. rosea: salidroside, rhodiolosides (B and C), rhodiosin, luteolin, catechin, quercetin, quercitrin, herbacetin, sacranoside A, vimalin, and others. In addition to the reported metabolites, 29 metabolites were newly annotated in Rh. rosea. There were flavonols: dihydroquercetin, acacetin, mearnsetin, and taxifolin-O-pentoside; flavones: apigenin-O-hexoside derivative, tricetin trimethyl ether 7-O-hexosyl-hexoside, tricin 7-O-glucoronyl-O-hexoside, tricin O-pentoside, and tricin-O-dihexoside; flavanones: eriodictyol-7-O-glucoside; flavan-3-ols: gallocatechin, hydroxycinnamic acid Caffeoylmalic Acid, and di-O-caffeoylquinic acid; coumarins: esculetin; esculin: fraxin; and lignans: hinokinin, pinoresinol, L-ascorbic acid, glucaric acid, palmitic acid, and linolenic acid. The results of supercritical CO(2)-extraction from roots and rhizomes of Rh. rosea, in particular, indicate that the extract contained all biologically active components of the plant, as well as inert mixtures of extracted compositions.

Phenolic profile, safety assessment, and anti-inflammatory activity of Salvia verbenaca L.[Pubmed:33631275]

J Ethnopharmacol. 2021 May 23;272:113940.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia species are known to have anti-inflammatory properties, and are traditionally used for healing purposes. Salvia verbenaca is an Algerian plant used for healing wounds and ulcers. AIM OF THE STUDY: This work aims to assess the acute and subacute safety of S. verbenaca and its possible anti-inflammatory activity as a mechanism contributing to its traditional applications. MATERIALS AND METHODS: Lethal toxicity of S. verbenaca hydromethanolic extract was evaluated against Artemia salina larvae, while acute and subacute toxicity were orally tested on mice. The anti-inflammatory activity was screened ex vivo using membrane stabilization and in vivo using xylene induced ear edema as an acute inflammation model. The antiradical, reducing power and iron chelating activities of S. verbenaca were also investigated in vitro, and phenolic compounds were determined using UHPLC-DAD-ESI-MS(n)(.) RESULTS: Salvia verbenaca extract contained high amounts of phenolic compounds (206 mug GAE/mg extract). The in vitro antioxidant activity showed promising radical scavenging ability, iron chelating (IC(50): 189 mug/mL), reducing power and strong anti-lipid-peroxidation effect (IC(50): 111 mug/mL). The extract had potential cytotoxic effect against Artemia salina larvae (LC(50): 30 mug/mL), but did not exhibit any acute/subacute toxicity effect on mice. Salvia verbenaca inhibited hypotonic and heat induced hemolysis and also reduced 50% of xylene induced ear edema at 600 mg/kg bw. Rosmarinic acid and Caffeoylmalic Acid were identified as the major compounds. CONCLUSION: Salvia verbenaca hydromethanolic extract was found to be safe at acute and subacute levels. Its in vitro/in vivo antioxidant activity, membrane stabilizing properties and anti-inflammatory activity may be an important aspect of its wound healing and anti-ulcer traditional use.

Phytochemical Profile and Biological Activities of Crude and Purified Leonurus cardiaca Extracts.[Pubmed:33494336]

Plants (Basel). 2021 Jan 21;10(2):195.

Leonurus cardiaca L. (Lamiaceae) is a perennial herb distributed in Asia and Southeastern Europe and has been used in traditional medicine since antiquity for its role against cardiac and gynecological disorders. The polar extracts obtained from L. cardiaca aerial parts contain several compounds among which alkaloids, iridoids, labdane diterpenes, and phenylethanoid glycosides play a major role in conferring protection against the aforementioned diseases. On the other hand, the antioxidant activities and the enzyme inhibitory properties of these extracts have not yet been deeply studied. On the above, in the present study, crude and purified extracts were prepared from the aerial parts of L. cardiaca and have been chemically characterized by spectrophotometric assays and HPLC-DAD-MS analyses. Notably, the content of twelve secondary metabolites, namely phenolic acids (chlorogenic, caffeic, caffeoylmalic and trans-ferulic acids), flavonoids (rutin and quercetin), phenylethanoid glycosides (verbascoside and lavandulifolioside), guanidine pseudoalkaloids (leonurine), iridoids (harpagide), diterpenes (forskolin), and triterpenes (ursolic acid), has been determined. Furthermore, the extracts were tested for their antioxidant capabilities (phosphomolybdenum, DPPH, ABTS, FRAP, CUPRAC, and ferrous chelating assays) and enzyme inhibitory properties against cholinesterase, tyrosinase, amylase, and glucosidase. The purified extracts contained higher phytochemical content than the crude ones, with Caffeoylmalic Acid and verbascoside as the most abundant compounds. A linear correlation between total phenolics, radical scavenging activity, and reducing power of extracts has been found. Notably, quercetin, caffeic acid, lavandulifolioside, verbascoside, chlorogenic acid, rutin, and ursolic acid influenced the main variations in the bioactivities found in L. cardiaca extracts. Our findings provide further insights into the chemico-biological traits of L. cardiaca and a scientific basis for the development of nutraceuticals and food supplements.

Impact of Household Cooking Techniques on African Nightshade and Chinese Cabbage on Phenolic Compounds, Antinutrients, in vitro Antioxidant, and beta-Glucosidase Activity.[Pubmed:33409289]

Front Nutr. 2020 Dec 21;7:580550.

Different household cooking techniques (boiling, steaming, stir frying, and microwave) were tested on the changes of targeted phenolic compounds, antioxidant property (ferric reducing-antioxidant power (FRAP) activity), alpha-glucosidase activity, antinutritive compounds, and sensory properties in commonly consumed traditional leafy vegetables in Southern Africa, the non-heading Chinese cabbage (Brassica rapa L. subsp. chinensis) and African nightshade (Solanum retroflexum Dun). Stir frying increased kaempferol-3-O-hydroxyferuloyl-trihexoside, kaempferol-dihexoside, sinapoyl malate, rutin, and isorhamnetin-O-dihexoside in Chinese cabbage leaves, followed by steaming. Similarly, stir frying increased kaempferol-3-O-rutinoside, chlorogenic acid, Caffeoylmalic Acid, and quercetin-3-O-xylosyl-rutinoside in nightshade, followed by steaming. Biomarkers, sinapoyl malate (Chinese cabbage) and Caffeoylmalic Acid (nightshade), separated the stir frying from the other cooking techniques. Steaming and stir-frying techniques significantly increased the FRAP activity; whereas boiling and microwaving reduced the tannin, oxalate, and phytate contents in both leafy vegetables and steroidal saponins in nightshade. Stir-fried nightshade leaf extract showed the most effective inhibition against alpha-glucosidase activity, with an IC(50) of 26.4 mug ml(-1), which was higher than acarbose, a synthetic compound (positive control; IC(50) 69.83 mug ml(-1)). Sensory panelists preferred the stir-fried Chinese cabbage and nightshade leaves, followed by steamed, microwaved, and boiled vegetables.

Targeting fish spoilers Pseudomonas and Shewanella with oregano and nettle extracts.[Pubmed:32474229]

Int J Food Microbiol. 2020 Sep 2;328:108664.

To control Pseudomonas and Shewanella as important psychrotrophic spoilage bacteria in fish meat, we used ethanolic extracts of oregano (Origanum vulgare subsp. vulgare) and nettle (Urtica dioica), with phytochemical characterisation of the extracts and their bioactive compounds. Liquid chromatography coupled with photodiode array detection and electrospray ionisation-mass spectrometry was used for qualitative compositional determination of the extracts. Four main compounds were identified in the oregano extract, with rosmarinic acid the most abundant, followed by three glycosylated phenolics, one of which is reported for the first time in O. vulgare: 4'-O-beta-d-glucopyranosyl-3',4'-dihydroxybenzyl-4-hydroxybenzoate. Six main compounds were identified in the nettle extract, as Caffeoylmalic Acid and five flavonoid glycosides. These oregano and nettle ethanolic extracts showed in-vitro antimicrobial activities against selected Pseudomonas and Shewanella strains in broth and fish meat homogenate when evaluated at two inoculum concentrations. The antimicrobial activities were more pronounced for the nettle extract at the lower inoculum concentration, and for both the Shewanella strains. Growth inhibition in the fish meat homogenate was evaluated at 3.13 mg/mL and 1.56 mg/mL at 5  degrees C. Again, the nettle extract showed greater antimicrobial activity, which was seen as the lowest maximum growth rate, followed by the oregano extract, which was inhibitory only at 3.13 mg/mL. Finally, the extracts were applied to fish meat that was then stored at 5  degrees C for 9 days. Evaluation here was for the counts of the mesophilic, psychrotrophic, Pseudomonas and H(2)S producers. These confirmed the better antimicrobial effects of the nettle extract, especially against the H(2)S-producing bacteria, which included Shewanella. Both of the extracts were rich in glycosides of flavonoids and phenolic acids. The enzymatic activities of the Pseudomonas and Shewanella spoilage bacteria and their actions on the phenolic glycosides from natural sources will be further investigated.

Impact of moist cooking methods on colour, anti-nutritive compounds and phenolic metabolites in African nightshade (Solanum retroflexum Dun.).[Pubmed:32387944]

Food Chem. 2020 Apr 25;325:126805.

Not much information is available on the changes of phenolic metabolites or anti-nutritive compounds in African nightshade leaves during moist cooking. Blanching methods (boiling, microwave, and steaming) using 5-20% lemon juice was compared with the plain water as a control. Lemon juice at 20% significantly increased the total colour differences (DeltaE). Chlorophyll content and the overall acceptance were highest for samples steamed in 5% lemon juice. Steam blanching in plain water reduced the tannin, oxalate and phytate contents but showed higher comparative peak responses for steroidal saponins. Neochlorogenic, chlorogenic, and Caffeoylmalic Acid, kaempferol O-rhamnosyl hexoside, and rutin were identified blanched leaves. Principle component analysis (PCA) discriminated between blanching treatments while Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) showed clear group distinctions between the blanching treatments. Chlorogenic acid, neochlorogenic acid and cryptochlorogenic acid were the responsible biomarkers for the separation of the steam blanching treatments. Thus, steam blanching preserves the functional compounds in nightshade leaves.

Polyphenols from Salix tetrasperma Impair Virulence and Inhibit Quorum Sensing of Pseudomonas aeruginosa.[Pubmed:32187997]

Molecules. 2020 Mar 16;25(6):1341.

Bacterial resistance represents one of the emerging obstacles in plants, animals, and humans that impairs treatment with antibacterial agents. Targeting of the bacterial quorum sensing system is one of the strategies to overcome this problem. Recently, research has been focused on natural and food components which can function as quorum sensing inhibitors. In this study, a methanol extract from Salix tetrasperma stem bark was phytochemically profiled by LC-MS analysis. This resulted in the identification of 38 secondary metabolites with (epi)catechin-(epi)catechin, epicatechin, tremulacin, salicortin, and trichocarposide as the major constituents. The extracts of both stem bark and the previously profiled flower of S. tetrasperma were tested for anti-quorum sensing activity in a common and widely distributed pathogen Pseudomonas aeruginosa. The natural products inhibited swimming and swarming motilities, as well as proteolytic and hemolytic activities in a dose-dependent manner. Molecular docking of the constituents from both extracts against the quorum sensing controlling systems Lasl/LasR, rhll/rhlR, and PQS/MvfR showed that epicatechin, (epi)catechin-(epi)catechin, p-hydroxy benzoyl galloyl glucose, p-hydroxy benzoyl protocatechuic acid glucose, and Caffeoylmalic Acid could be the main active components. This study supports the importance of secondary metabolites, especially polyphenols, as quorum sensing inhibitors.