You are currently viewing a new version of our website. To view the old version click .
MDPIMDPI
Search all articles
Biomolecules
Download PDF
  • Review
  • Open Access

2 December 2022

Leucosceptosides A and B: Two Phenyl-Ethanoid Glycosides with Important Occurrence and Biological Activities

,
,
,
,
,
,
,
and
1
Dipartimento di Biologia Ambientale, Università di Roma “La Sapienza”, Piazzale Aldo Moro 5, 00185 Rome, Italy
2
NMR Lab, Università di Roma “La Sapienza”, Piazzale Aldo Moro 5, 00185 Rome, Italy
3
Dipartimento di Chimica, Università di Roma “La Sapienza”, Piazzale Aldo Moro 5, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Biomolecules2022, 12(12), 1807;https://doi.org/10.3390/biom12121807
Version Notes
Order Reprints

Abstract

In this review paper, the occurrence in the plant kingdom, the chemophenetic value and the biological activities associated with two specific phenyl-ethanoid glycosides, i.e., leucosceptoside A and leucosceptoside B, were reported. This is the first work ever conducted on such a subject. Analysis of the literature data clearly led to three important conclusions: leucosceptoside A is much more common in plants than leucosceptoside B; leucosceptoside A exerts more biological activities than leucosceptoside B even if nothing can be generally concluded about which one is actually the most potent; neither of these compounds can be used as a chemophenetic marker. These three aspects and more are discussed in more depth in this work.

1. Introduction

Leucosceptoside A and leucosceptoside B are two natural compounds belonging to the class of phenyl-ethanoid glycosides which have gained increasing attention in recent years due to their important and effective biological activities [1].
Phenyl-ethanoid glycosides are biosynthetically generated merging two different processes, the shikimic acid pathway, which produces the β-hydroxy-tyrosol part of phenyl-ethanoid glycosides, and the cinnamate pathway, which produces its caffeic acid part after a series of intermediate steps [2].
The base compound of phenyl-ethanoid glycosides is called verbascoside, acetoside or acteoside, which is structurally characterized by a central glucose residue linked to one β-hydroxy-tyrosol and one rhamnose residue through ether bonds, and to one caffeic acid through an ester bond. Leucosceptoside A differs from verbascoside for the substitution with a methyl group in the caffeic acid moiety. Indeed, leucosceptoside B differs from verbascoside for the substitution with one methyl group each in the caffeic acid and β-hydroxy-tyrosol moieties as well as for the substitution with one β-D-apiose residue in the position 6 of the glucose moiety [3] (Figure 1).
Figure 1. Structures of leucosceptoside A and leucosceptoside B.
In the literature, there are some review papers on phenyl-ethanoid glycosides in general, exploring mainly their occurrence, structure and biological activities [1,2,4]; however, no review paper has ever focused its complete attention on leucosceptoside A and leucosceptoside B, which have often been actually neglected regarding several of their aspects in the past reviews. In addition, some of these reviews are now outdated and do not cover the chemophenetics of these compounds or even of the phenyl-ethanoid glycosides in general. These represent the main reasons why this review paper was written. In this, the specific occurrence of leucosceptoside A and leucosceptoside B in the plant kingdom as well as their relative biological activities were reported with major details. In addition, chemophenetic conclusions on these compounds were drawn and a strict comparison on the biological activities of these two compounds in more senses was also performed, both for the first time. This review paper is based on all the published papers until now, as recovered from Scopus, Reaxys, Google Scholar and PubMed. Only works regarding plants were considered, thus, excluding cell cultures. In addition, only works without any kind of procedure possibly producing alterations and artifacts in the phytochemical pattern were cited. Lastly, papers not written in English were not considered.

2. Occurrence in the Plant Kingdom

In the following Tables, the occurrences of leucosceptoside A (Table 1) and leucosceptoside B (Table 2) in the plant kingdom are reported and divided according to the family of the plant they have been isolated from. These tables are sub-divided according to the plant species and report data on the collection area of the plant cited, the studied organs and the methodologies of isolation and identification for these compounds. In the collection area columns, if not differently specified, the studied population or populations are intended to be collected from the wild.
Table 1. Occurrence of leucosceptoside A in the plant kingdom.
Table 2. Occurrence of leucosceptoside B in the plant kingdom.
Leucosceptoside A proved to be quite common in the plant kingdom. In fact, it has been evidenced in eleven families. In particular, its lowest occurrence was observed in Asteraceae, Malvaceae and Oleaceae with one report each. In contrast, the highest occurrence has been noticed in the Lamiaceae family with 69 reports even though these were singular reports in most cases. Nevertheless, it is important to underline that not all the genera in the Lamiaceae family have shown the presence of this compound. Within the Lamiaceae family, this compound has been found particularly in the Phlomis L. genus with 15 reports whereas it is quite rare in Betonica L., Schnabelia Hand.-Mazz. and Volkameria L. genera with only one report of its presence each. Henceforth, further phytochemical studies on species belonging to these genera are necessary in order to verify if this compound is really part of their phytochemical components or if its presence was only accidental. All the other seven families see a moderate occurrence of leucosceptoside A. For what concerns the collection areas of the studied species, no significatively restricted zone for the occurrence of this compound has been observed since its presence has been found in species collected from four continents, i.e., America, Europe, Africa and Asia. Nothing can be stated at the moment about the Oceanian situation since no work on it has been found. As for the studied organs, leucosceptoside A has shown no particular preference for a specific accumulation site having been individuated in leaves, aerial parts, tubers, roots and the whole plant even if it seems this compound prefers aerial organs. A few procedures have been used to extract this compound mainly associated with maceration processes in their different forms. Indeed, several techniques have been used for its isolation and identification, including high performing liquid chromatography relative techniques, liquid chromatography relative techniques, thin-layer chromatography relative techniques, infrared, ultraviolet and nuclear magnetic resonance spectroscopies and mass spectrometry.
In the end, it is extremely relevant to highlight that Table 1 clearly indicates how leucosceptoside A cannot be used as a chemophenetic marker at any level since it has shown no specificity and also because the families where it was found are taxonomically very distant from each other.
With respect to leucosceptoside A, leucosceptoside B proved to be less common in the plant kingdom. In fact, it has been evidenced only in six families. Its lowest occurrence was observed in the Bignoniaceae, Orobanchaceae, Plantaginaceae and Verbenaceae families with one report each, whereas the highest occurrence has been noticed in the Lamiaceae family again with seventeen reports. There is a certain parallelism between the results found for leucosceptoside A and those found for leucosceptoside B for what concerns the collection areas of the studied species, the studied organs and the methodologies adopted for their isolation and identification. Indeed, there are some important differences for what concerns the families, genera and species where their presence has been reported. In particular, leucosceptoside B has not been reported in the Acanthaceae, Compositae, Linderniaceae, Malvaceae and Oleaceae families. In addition, for what concerns the Bignoniaceae, Scrophulariaceae and Verbenaceae families, leucosceptoside B has been found in completely different species, if not genera themselves, than leucosceptoside A. For what concerns the Lamiaceae family, the reported genera and species are not generally the same as for leucosceptoside A. In particular, leucosceptoside B has not been found in the Betonica L., Caryopteris Bunge, Clerodendrum L., Galeopsis L., Lagopsis Bunge, Leonurus L., Salvia L., Scutellaria L., Sideritis L. and Volkameria L. genera. This situation prompts the need to perform more phytochemical analyses on the species for its further research, also because several singular reports have been found in the literature with the same conclusions as drawn before.
Leucosceptoside B cannot also be used as a chemophenetic marker at any level for the same reasons as presented before, even if it presents a lower occurrence than leucosceptoside A.

3. Biological Activities

3.1. Leucosceptoside A

Leucosceptoside A has shown several interesting pharmacological activities. In the following lines, these activities are explored and detailed one-by-one.

3.1.1. Antioxidant and Radical Scavenging Activity

Leucosceptoside A proved to be a good antioxidant compound. Several studies against DPPH.+ confirm this with quite similar efficacy values. In particular, Ersöz et al. [58] obtained an IC50 value of 76.0 µM, which is lower than ascorbic acid used as a positive control (IC50 = 112 µM). Harput et al. [7] observed an IC50 value of 18.43 μg/mL, which is higher than quercetin but comparable (IC50 = 4.3 µg/mL), whereas Ono et al. [154] obtained an EC50 value of 25.7 µM, which is very similar to that for α-tocopherol (EC50 = 25.9 µM). Huang et al. [150] obtained an IC50 value of 72.14 μM, which is lower than vitamin C (IC50 = 81.83 µM). Lan et al. [117] obtained an EC50 value of 11.26 μM, which is slightly better than the positive control, ascorbic acid (EC50 value of 12.29 μM). Indeed, Calis et al. [60] obtained an IC50 value of 125.4 µM, which is quite higher than that of dl-α-tocopherol, used as a positive control (IC50 = 75.5 µM). Delazar et al. [61] obtained an RC50 of 0.0148 mg/mL, which is higher than trolox and quercetin, used as positive controls (RC50 values of 0.00307 and 0.0000278 mg/mL), instead. Lastly, Shen et al. [13] obtained an IC50 value of 53.32 µM, which was found to be higher than that of BHT, but no value of this latter was given.
On the other hand, Charami et al. [86] expressed the results as percentages of inhibition, which were 88.3% and 89.0% after 20 and 60 min, respectively, at the concentration of 0.1 mM, whereas the positive control acetyl salicylic, at the same concentration and times, showed a percentage of inhibition of 80.6%. Additionally, Harput et al. [54] expressed their results as percentages of inhibition and compared their results with three positive controls. In particular, the value for leucosceptoside A was 41.8% at the concentration of 200 µM, which is near to ascorbic acid and BHA (percentages of inhibition equal to 39.9 and 35.6%, respectively) but worse than chlorogenic acid (percentage of inhibition equal to 68.6%).

3.1.2. Radical Scavenging

Leucosceptoside A was observed to be a modest radical scavenging compound. In particular, Wang et al. [112] studied the scavenging properties of this compound with respect to superoxide anion and obtained a SC50 of 0.294 mM, which is higher than all the other phenyl-ethanoid glycosides studied in this work. The best one was verbascoside, which presents an SC50 value of 0.063 mM. In addition, Wang et al. [112] also studied the antioxidant potential of this compound through a luminol-enhanced chemiluminescence assay against N-formyl-methionyl-leucyl-phenylalanine in stimulated human polymorphonuclear neutrophils. The results showed that this compound is a weak inhibitor of hydroxyl radicals with a percentage of inhibition of 27.8% at the concentration of 0.55 mM and a modest iron reductor with a percentage of 17.86% at the concentration of 1.57 mM. The former value represents the lowest percentage of inhibition among all the phenyl-ethanoid glycosides considered in this study, whereas the latter value is the second worst. Verbascoside was the most active as an inhibitor of the hydroxyl radical with a percentage of 55.7% at the concentration of 0.55 mM, whereas pedicularioside M was the most active as an iron reductor with a percentage of 23.57% at the concentration of 1.73 mM. Heilmann et al. [185] also studied the radical scavenging effects of this compound in N-formyl-methionyl-leucyl-phenylalanine-stimulated human polymorphonuclear neutrophils through a luminol-enhanced chemiluminescence assay. The obtained IC50 value was 0.18 µM, which is higher but not too far from that of quercetin used as a positive control (IC50 value = 0.5 µM). Nevertheless, most of the other phenyl-ethanoid glycosides studied in this work showed better results than leucosceptoside A and, in particular, echinacoside was the best one with an IC50 value of 0.03 µM.

3.1.3. Anti-Inflammatory Activity

Leucosceptoside A shows moderate anti-inflammatory activities with respect to NO production. In particular, Han et al. [151] obtained an IC50 value of 9.0 µM in the Raw 264.7 cell line, whereas the positive control aminoguanidine had an IC50 value of 10.7 µM. Vien et al. [14] obtained a different result in LPS-stimulated BV2 microglial cells using the Griess assay, with an IC50 value of 61.1 µM, which is much higher than the positive control butein (IC50 = 4.5 µM). In contrast, Ochi et al. [147] obtained a moderate percentage of inhibition of 40% in cell culture supernatants of LPS-stimulated RAW264.7 macrophages at the concentration of 100 µM, whereas the positive control L-NMMA presents an inhibition value of 55% at the same concentration.

3.1.4. Enzyme Inhibitory Activity

Leucosceptoside A has been also studied for its potential inhibitory effects on some enzymes, i.e., α-glucosidase, acetylcholinesterase, protein kinase C alpha and tyrosinase.
Concerning α-glucosidase, this compound has shown contrasting results. In fact, Liu et al. [27] obtained an IC50 value of 0.7 mM, which is much lower than acarbose used as a positive control (IC50 = 14.4 mM). Indeed, Thu et al. [146] obtained an IC50 value of 273.0 µM, which is a little higher than that of acarbose (IC50 = 204.2 µM).
Leucosceptoside A also possesses between moderate and modest acetylcholinesterase inhibitory effects. In fact, Kang et al. [33] obtained an IC50 value of 423.7 µg/mL, which is much higher than Captopril® used as a positive control (IC50 value of 20 nM). In addition, Saidi et al. [186] obtained an IC50 value of 72.85 µM, which is also much higher than that of the positive control used in this study, i.e., galantamine (IC50 value of 4.14 µM). Indeed, Li et al. [187], using the Scheffe’s test, obtained an IC50 value of 3.86 mM, which is comparable to that of Captopril® used again as a positive control (IC50 value of 2.11 nM).
This compound is also a modest protein kinase C alpha inhibitor with an IC50 value of 19.0 µM. This value is good in number but, in the same study, other phenyl-ethanoid glycosides were found to be more active, such as forsythoside and verbascoside, showing IC50 values of 4.6 and 9.3 µM, respectively [131].
In addition, this compound shows only modest tyrosinase inhibitory activities, with a percentage of inhibition of 21.65% at the concentration of 0.051 mM. Kojic acid, used as a positive control, has a percentage of inhibition of 53.87% at the concentration of 0.047 mM [188]. A similar result was obtained by Saidi et al. [186], who observed a percentage of inhibition of 39.5% at the concentration of 100 µM, whereas the positive control hydroquinone has a percentage of inhibition of 72.0% at the same concentration.
Lastly, this compound has shown no effect on the hyaluronidase enzyme inhibition test and collagenase enzyme inhibition test at the concentration of 100 µg/mL [138].

3.1.5. Hepatoprotective Activity

At 100 µM, leucosceptoside A exerts strong hepatoprotective properties in pretreatment as obtained by studying the viability of HepG2 cells after CCl4 intoxication, by means of an MTT assay and flow cytometry, with values of cell number and cell viability both above 80%, thus, implying a restoration of cell survival. These values are extremely good in numbers, but no standard compound was tested for comparison. The mechanism of action occurs through the inhibition of NF-kB activation since it was observed that pretreatment with this compound can inhibit CCl4-induced lipid peroxidation in HepG2 cells by 177.73% and attenuate the decrease in SOD by 76.58%; furthermore, pre-incubation of the same cells with this compound can prevent ROS production by 183.56% [13].

3.1.6. Neuroprotective Activity

Leucosceptoside A, in pretreatment, exerts good neuroprotective effects against the 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death in mesencephalic neurons of rats. MPP+ is the ion produced after the biotransformation of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the monoamine oxidase B, and it is well known to cause Parkinson’s disease in rats and non-human primates. By means of an MTT assay, it was observed that leucosceptoside A, at the concentration of 4 µM, reduces cell death by 7%, whereas at the concentration of 16 µM, it increases cell growth by 3.7%. These values are extraordinary, however, in the same study, a more efficient compound was found, i.e., pedicularioside A. In fact, at the concentration of 4 µM, this latter compound shows a reduction value of cell death by 3.4% and, at the concentration of 16 µM, it increases cell growth by 21.4% [189].

3.1.7. Cytoprotective Activity

Leucosceptoside A exhibits promising cytoprotective effects against t-BHP-induced toxicity in HepG2 cells with an IC50 value of 21.1 µM. This value is lower than silymarin used as a positive control (IC50 = 37.1 µM) [23].

3.1.8. Anticomplementary Activity

Leucosceptoside A exerts good anticomplementary effects with a CH50 value of 0.23 mM, which is slightly higher than that of the standard compound heparin (CH50 = 0.06 mM) [119].

3.1.9. Anti-HIV Activity

Leucosceptoside A has shown strong HIV-1 integrase inhibitory effects with an IC50 value of 29.4 µM. This value is better than curcumin (IC50 = 54.3 µM) and comparable to L-chicoric acid (IC50 = 21.0 µM) used as positive controls [32].

3.1.10. Cytotoxic Activity

According to Argyropoulou et al. [46], leucosceptoside A exerts very modest cytotoxic effects on HeLa (human epithelial carcinoma), MCF7 (breast metastatic adenocarcinoma) and HC7-116 (colon cancer) cell lines with IC50 values of 200, 189.08 and 182.33 µg/mL, respectively. The standard compound doxorubicin presents IC50 values of 0.175, 0.235 and 0.096 µg/mL, respectively, whereas the other standard compound actinomycin D presents IC50 values of 0.013, 0.022 and 0.019µg/mL, respectively. On the contrary, it showed no effect against melanoma. Saidi et al. [186] also tested the cytotoxic effects of this compound on HeLa cell lines obtaining an IC50 = 80.87 µM as well as a positive result on the A549 (adenocarcinomic human alveolar basal epithelial cells) cancer cell line obtaining an IC50 = 99.00 µM. All these values are much higher than the standard compounds used, i.e., doxorubicin for the former cancer cell line (IC50 = 0.36 µM) and ellipticine for the latter cancer cell line (IC50 = 0.31 µM). Abe et al. [159] obtained promising results on Hela (GI50 = 42 µM) and also against the B16F10 (murine melanoma) cell line with a GI50 value equal to 28 µM and against the MK-1 (gastric carcinoma with liver metastasis) cell line with a GI50 value equal to 33 µM. All these values are good in numbers, but some other phenyl-ethanoid glycosides studied in this work present better results in full or in part. In particular, iso-verbascoside was the most potent against B16F10 and MK-1 with GI50 values of 10 and 32 µM, respectively, whereas arenarioside was the most potent against HeLa with a GI50 value of 34 µM. Unlike the previous works, Saracoglu et al. [49] did not observe any effect on HeLa cells for this compound and this contrast all depends on the methodology adopted. Saracoglu et al. [49] did not observe any effect against dRLh-88 (rat hepatoma), P-388-d1 (mouse lymphoid neoplasma) and S-180 (sarcoma) cancer cell lines, too.

3.1.11. Inhibitory Activities

Leucosceptoside A exhibits good inhibitory effects against ADP + NADPH-induced lipid peroxidation in rat liver microsomes with an IC50 value of 1.69 µM, which is very promising. Yet, other phenyl-ethanoid glycosides studied in this work showed better results. In particular, iso-verbascoside was the most potent with an IC50 value of 0.38 µM [132].
This compound also exhibits inhibitory effects on the protonation of thymine radical anion induced by pulse radiolysis, which causes severe damages in cells with a reaction rate constant of electronic transfer equal to 1.54 × 109 dm3 mol−1 s−1. This value is very good in number, but without a direct comparison with any compound [190].

3.1.12. Antimicrobial Activities

Leucosceptoside A exerts poor antimicrobial effects against Staphylococcus aureus ATCC29213 and Enterococcus faecalis ATCC29212 with MIC values of 1000 µg/mL [60]. These values are extremely high and are generally considered to be inactive.
Indeed, it has shown no activity against Escherichia coli ATCC25922 [60], Mycobacterium tuberculosis H37Rv [30], Pseudomonas aeruginosa ATCC27853 [60], Bacillus subtilis NBRC3134 and Klebsiella pneumoniae NBRC3512 [24].

3.1.13. Antifungal Activities

Leucosceptoside A has shown no activity against Candida albicans ATCC90028, Candida krusei ATCC6258 and Candida parapsilosis ATCC22019 [60].

3.2. Leucosceptoside B

Leucosceptoside B has also shown some interesting pharmacological activities, even if less numerous than leucosceptoside A. In the following lines, these activities are explored and detailed one-by-one.

3.2.1. Antioxidant Activity

Leucosceptoside B proved to be an antioxidant compound. Several studies, according to different assays, confirm this with opposite efficacy values.
According to the DPPH.+ assay, this compound exerts between moderate and modest effects. In fact, Niu et al. [166] obtained an IC50 value of 31.16 µM, which is higher than ascorbic acid used as a positive control (IC50 = 7.81 µM). In addition, Georgiev et al. [182] obtained an IC50 value of 96 µg/mL, which is high with respect to the other phenyl-ethanoid glycosides studied in this work. In particular, this compound was found to be the weakest, whereas the most potent was forsythoside B with an IC50 value of 21 µg/mL. Indeed, Lan et al. [117] obtained an EC50 value of 13.05 μM, which is comparable to that of ascorbic acid (EC50 value of 12.29 μM). Lastly, Calis et al. [60] obtained an IC50 value of 61.3 µM, which is lower than that of dl-α-tocopherol used as a positive control (IC50 = 75.5 µM); yet there was one phenyl-ethanoid glycosides (myricoside) that is even more potent than this (IC50 = 46.8 µM).

3.2.2. Radical Scavenging Activity

Through a luminol-enhanced chemiluminescence assay with formyl-methionyl-leucyl-phenylalanine in stimulated human polymorphonuclear neutrophils, Heilmann et al. [185] reported the radical scavenging activities of this compound with an IC50 value of 0.17 µM, which is higher but not too far from that of quercetin used as a positive control (IC50 value = 0.5 µM).
Indeed, Georgiev et al. [182] also studied the ORAC, HORAC, FRAP and superoxide anion activities of this compound obtaining different results. In particular, good effects were observed for the first one with a value of 16264.7 ORACFL/g, which is higher than chlorogenic acid used as a standard compound (9172.8 ORACFL/g), and for the second one with a value of 3885.1 HORACFL/g, which is higher than chlorogenic acid used as a standard compound (3584.5 ORACFL/g). Conversely, poor effects were observed for the third assay with a value of absorbance of 0.602 at 700 nm, which is much lower than chlorogenic acid used as a reference compound (3.547), whereas moderate effects were observed for the last assay with an IC50 value of approximately 45 µg/mL, which is much higher with respect to the other phenyl-ethanoid glycosides studied in this work, and in particular, of verbascoside, which was the best one (IC50 = 4.2 µg/mL).

3.2.3. Anti-Inflammatory Activity

Leucosceptoside B exerts good inhibitory effects on cobra venom factor-induced alternative pathway activation in mouse sera with a percentage of inhibition of 40% and on COX-2 production with a percentage of inhibition near 30%. The positive control, indomethacin, presents a percentage of inhibition near 70%. In addition, it shows moderate inhibitory effects on NO production and IL-10 production as well as good inhibitory effects on COX-1, even if in the study, the values were not clearly expressed. Furthermore, all these values are higher than indomethacin [183].

3.2.4. Enzyme Inhibitory Activity

Georgiev et al. [182] studied the acetylcholinesterase and butyrylcholinesterase inhibitory activities of leucosceptoside B. In both cases, the activity is dose-dependent; however, in the former, the percentage of inhibition is almost 50% at the concentration of 100 µg/mL, whereas in the latter, the percentage of inhibition is a little above 10% at the concentration of 100 µg/mL. These values are much lower than the positive control galanthamine, which presents percentages of inhibition of 98.97 and 89.95%, respectively, at the same concentrations.
Indeed, Cespedes et al. [191] obtained a different result for the acetylcholinesterase inhibitory effects of this compound with an IC50 value of 20.1 µg/mL, whereas galanthamine has an IC50 value of 13.2 µg/mL.
Cespedes et al. [191] did not observe any butyrylcholinesterase inhibitory activity for leucosceptoside B.

3.2.5. Neuroprotective Activity

Leucosceptoside B, in pretreatment, is also able to exert strong neuroprotective effects against the 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death in mesencephalic neurons at the concentration of 40 µg/mL. The potency was measured as optical density with a value of 1.06. However, buddleoside A, another phenyl-ethanoid glycoside, was found to be much more potent with a value of 1.62 [149].

3.2.6. Inhibitory Activities

Leucosceptoside B has shown no human lactate dehydrogenase inhibitory activity [172].

3.2.7. Antimicrobial Activity

Leucosceptoside B has shown very poor antimicrobial effects against Staphylococcus aureus ATCC29213 and Enterococcus faecalis ATCC29212 with MIC values of 1000 µg/mL [60]. Again, these values are extremely high and are generally considered to be inactive.
In addition, it has proven to be inactive against Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC27853 [60].

3.2.8. Antimicrobial Activity

Leucosceptoside B has shown no antifungal activity against Candida albicans ATCC90028, Candida krusei ATCC6258 and Candida parapsilosis ATCC22019 [60].

3.3. Comparing the Biological Results of Leucosceptosides A and B

Table 3 and Table 4 below summarize the biological activities and efficacy values of leucosceptoside A and leucosceptoside B, respectively.
Table 3. Summary of the biological activities and efficacy values of leucosceptoside A.
Table 4. Summary of the biological activities and efficacy values of leucosceptoside B.
According to the data as reported in Section 3.1 and Section 3.2 and Table 3 and Table 4, leucosceptoside A proved to be a more important biological compound than leucosceptoside B based on the number of biological assays performed on them. In fact, leucosceptoside A has been tested for more numerous biological assays than leucosceptoside B (10 vs. 5). In particular, leucosceptoside A was also tested for its hepatoprotective, cytoprotective, cytotoxic, anticomplementary and anti-HIV activities with respect to leucosceptoside B. This minor number of assays performed on leucosceptoside B may be explained not only by its minor occurrence in the plant kingdom but also for the fact that this compound is much more difficult to isolate in pure form since its co-elution with more polar compounds than phenyl-ethanoid glycosides is extremely common. On the contrary, given the literature data results, it is not so easy to ascertain which compound is generally the most efficient. This is due to the fact that leucosceptoside A and leucosceptoside B were directly compared only in two cases. The first case regards the radical scavenging effects of these compounds in formyl-methionyl-leucyl-phenylalanine-stimulated human polymorphonuclear neutrophils through a luminol-enhanced chemiluminescence assay and showed that leucosceptoside A and leucosceptoside B basically have the same efficacy (IC50 values of 0.18 µM vs. 0.17 µM) [185]. The second case regards the DPPH.+ radical scavenging assay and showed that leucosceptoside A is slightly better than leucosceptoside B (EC50 values of 11.26 µM vs. 13.05 µM) [117]. One further indirect comparison of the efficacy values of these two compounds can be made also according to the DPPH.+ radical scavenging assay; however, the relative studies led to extremely contrasting results. In fact, the IC50 values found for leucosceptoside A were 76.0 µM [58], 18.43 µM [7], 72.14 µM [150], 125.4 µM [60] and 53.32 µM [13], whereas the IC50 values found for leucosceptoside B were 31.16 µM [166], 96.0 µM [182] and 61.3 µM [60]. These discrepancies are due to several intrinsic methodological factors and are also dependent on the fact that leucosceptosides A and B were not studied together in these works. In this context, these results do not really allow to make any general conclusion on which of these compounds is the most potent. Indeed, for what concerns the rest of the biological activities, no comparison can be made since the two compounds were not studied together, different protocols were used, and the values were expressed in different unities of efficacy. These last aspects are certainly something to keep in consideration for future research in order to improve this situation.

4. Conclusions

This review article clearly shows how leucosceptoside A and leucosceptoside B are important compounds with regards to some aspects. In fact, they have been found in different species belonging to several families and, even though they do not possess chemophenetic significance on their own, they are also endowed with several interesting pharmacological activities including antioxidant, anti-inflammatory, enzyme inhibitory and neuroprotective. However, searching for these phytochemical components of plants is still quite limited due to the several factors. This review article also aimed to be a stimulus to amplify studies on both phytochemistry and pharmacology since there is still a lot to be discovered.

Author Contributions

Conceptualization, C.F.; Research, All the authors; Data curation, All the authors; Writing—original draft preparation, review and editing, All the authors. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Wu, L.; Georgiev, M.I.; Cao, H.; Nahar, L.; El-Seedi, H.-R.; Sarker, S.D.; Xiao, J.; Lu, B. Therapeutic potential of phenylethanoid glycosides: A systematic review. Med. Res. Rev. 2020, 40, 2605–2649. [Google Scholar] [CrossRef] [PubMed]
  2. Heldt, H.W.; Heldt, F. Phenylpropanoids comprise a multitude of plant secondary metabolites and cell wall components. In Plant Biochemistry, 3rd ed.; Elsevier Academic Press: San Diego, CA, USA, 2005; pp. 435–454. [Google Scholar]
  3. Tian, X.-Y.; Li, M.-X.; Lin, T.; Qiu, Y.; Zhu, Y.-T.; Li, X.-L.; Tao, W.-D.; Wang, P.; Ren, X.-X.; Chen, L.-P. A review on the structure and pharmacological activity of phenylethanoid glycosides. Eur. J. Med. Chem. 2021, 209, 112563. [Google Scholar] [CrossRef]
  4. Jiménez, C.; Riguera, R. Phenylethanoid glycosides in plants: Structure and biological activity. Nat. Prod. Rep. 1994, 11, 591–606. [Google Scholar] [CrossRef]
  5. Kanchanapoom, T.; Kasai, R.; Picheansoonthon, C.; Yamasaki, K. Megastigmane, aliphatic alcohol and benzoxazinoid glycosides from Acanthus ebracteatus. Phytochemistry 2001, 58, 811–817. [Google Scholar] [CrossRef] [PubMed]
  6. Prasansuklab, A.; Tencomnao, T. Acanthus ebracteatus leaf extract provides neuronal cell protection against oxidative stress injury induced by glutamate. BMC Complement. Altern. Med. 2018, 18, 278. [Google Scholar] [CrossRef] [PubMed]
  7. Harput, U.S.; Arihan, O.; Iskit, A.B.; Nagatsu, A.; Saracoglu, I. Antinociceptive, free radical-scavenging, and cytotoxic activities of Acanthus hirsutus Boiss. J. Med. Food 2011, 14, 767–774. [Google Scholar] [CrossRef] [PubMed]
  8. Noiarsa, P.; Ruchirawat, S.; Kanchanapoom, T. Acanmontanoside, a new phenylethanoid diglycoside from Acanthus montanus. Molecules 2010, 15, 8967–8972. [Google Scholar] [CrossRef]
  9. Ashour, M.A.-G. Isolation, HPLC/UV characterization and antioxidant activity of phenylethanoids from Blepharis edulis (Forssk.) Pers. growing in Egypt. Bull. Fac. Pharm. Cairo Univ. 2012, 50, 67–72. [Google Scholar] [CrossRef]
  10. Vo, T.N.; Nguyen, P.L.; Tran, T.T.N.; Nguyen, K.P.P.; Nguyen, N.S. Some phenylethanoids from roots of Pseuderanthemum carruthersii (Seem.) Guill var. atropurpureum (Bull.) Fosb. Vietnam J. Chem. 2010, 48, 325–331. [Google Scholar]
  11. Piccinelli, A.L.; De Simone, F.; Passi, S.; Rastrelli, L. Phenolic constituents and antioxidant activity of Wendita calysina leaves (Burrito), a folk Paraguayan tea. J. Agric. Food Chem. 2004, 52, 5863–5868. [Google Scholar] [CrossRef] [PubMed]
  12. Kanchanapoom, T.; Kasai, R.; Yamasaki, K. Lignan and phenylpropanoid glycosides from Fernandoa adenophylla. Phytochemistry 2001, 57, 1245–1248. [Google Scholar] [CrossRef] [PubMed]
  13. Shen, T.; Li, X.; Hu, W.; Zhang, L.; Xu, X.; Wu, H.; Ji, L. Hepatoprotective effect of phenylethanoid glycosides from Incarvillea compacta against CCl4-induced cytotoxicity in HepG2 cells. J. Korean Soc. Appl. Biol. Chem. 2015, 58, 617–625. [Google Scholar] [CrossRef]
  14. Ihtesham, Y.; Khan, U.; Dogan, Z.; Kutluay, V.M.; Saracoğlu, I. Evaluation of some biological effects of Incarvillea emodi (Royle ex Lindl.) Chatterjee and determination of its active constituents. Kafkas Univ. Vet. Fak. Derg. 2019, 25, 171–178. [Google Scholar]
  15. Arevalo, C.; Ruiz, I.; Piccinelli, A.L.; Campone, L.; Rastrelli, L. Phenolic derivatives from the leaves of Martinella obovata (Bignoniaceae). Nat. Prod. Commun. 2011, 6, 957–960. [Google Scholar] [CrossRef] [PubMed]
  16. Vien, L.T.; Hanh, T.T.H.; Quang, T.H.; Cuong, N.T.; Cuong, N.X.; Oh, H.; Sinh, N.V.; Nam, N.H.; Minh, C.V. Phenolic glycosides from Oroxylum indicum. Nat. Prod. Res. 2022, 36, 2336–2340. [Google Scholar] [CrossRef]
  17. Kanchanapoom, T.; Kasai, R.; Yamasaki, K. Phenolic glycosides from Barnettia kerrii. Phytochemistry 2002, 59, 565–570. [Google Scholar] [CrossRef]
  18. Plaza, A.; Montoro, P.; Benavides, A.; Pizza, C.; Piacente, S. Phenylpropanoid glycosides from Tynanthus panurensis: Characterization and LC-MS quantitative analysis. J. Agric. Food Chem. 2005, 53, 2853–2858. [Google Scholar] [CrossRef]
  19. Çalis, I.; Başaran, A.; Saracoğlu, I.; Sticher, O. Iridoid and phenylpropanoid glycosides from Stachys macrantha. Phytochemistry 1992, 31, 167–169. [Google Scholar] [CrossRef]
  20. Yuan, J.-Q.; Qiu, L.; Zouc, L.-H.; Wei, Q.; Miao, J.-H.; Yao, X.-S. Two new phenylethanoid glycosides from Callicarpa longissima. Helv. Chim. Acta 2015, 98, 482–489. [Google Scholar] [CrossRef]
  21. Wang, J. N-butanol-soluble chemical constituents from Callicarpa nudiflora. Chin. Pharm. J. 2017, 24, 1983–1987. [Google Scholar]
  22. Zhao, D.P.; Matsunami, K.; Otsuka, H. Iridoid glucoside, (3R)-oct-1-en-3-ol glycosides, and phenylethanoid from the aerial parts of Caryopteris incana. J. Nat. Med. 2009, 63, 241–247. [Google Scholar] [CrossRef] [PubMed]
  23. Park, S.; Son, M.J.; Yook, C.-S.; Jin, C.; Lee, Y.S.; Kim, H.J. Chemical constituents from aerial parts of Caryopteris incana and cytoprotective effects in human HepG2 cells. Phytochemistry 2014, 101, 83–90. [Google Scholar] [CrossRef]
  24. Yoshikawa, K.; Harada, A.; Iseki, K.; Hashimoto, T. Constituents of Caryopteris incana and their antibacterial activity. J. Nat. Med. 2014, 68, 231–235. [Google Scholar] [CrossRef]
  25. Nugroho, A.; Lee, S.K.; Kim, D.; Choi, J.S.; Park, K.-S.; Song, B.-M.; Park, H.-J. Analysis of essential oil, quantification of six glycosides, and nitric oxide synthase inhibition activity in Caryopteris incana. Nat. Prod. Sci. 2018, 24, 181–188. [Google Scholar] [CrossRef]
  26. Li, Y.B.; Li, J.; Li, P.; Tu, P.F. Isolation and characterization of phenylethanoid glycosides from Clerodendron bungei. Acta Pharm. Sin. 2005, 40, 722–727. [Google Scholar]
  27. Liu, Q.; Hu, H.-J.; Li, P.-F.; Yang, Y.-B.; Wu, L.-H.; Chou, G.-X.; Wang, Z.-T. Diterpenoids and phenylethanoid glycosides from the roots of Clerodendrum bungei and their inhibitory effects against angiotensin converting enzyme and α-glucosidase. Phytochemistry 2014, 103, 196–202. [Google Scholar] [CrossRef] [PubMed]
  28. Gao, L.M.; Wei, X.M.; He, Y.Q. Studies on chemical constituents in leaves of Clerodendron fragrans. China J. Chin. Mat. Med. 2003, 28, 948–951. [Google Scholar]
  29. Uddin, J.; Çiçek, S.S.; Willer, J.; Shulha, O.; Abdalla, M.A.; Sönnichsen, F.; Girreser, U.; Zidorn, C. Phenylpropanoid and flavonoid glycosides from the leaves of Clerodendrum infortunatum (Lamiaceae). Biochem. Syst. Ecol. 2020, 92, 104131. [Google Scholar] [CrossRef]
  30. Yadav, A.K.; Gupta, M.M. Quantitative determination of bioactive phenylethanoid glycosides in Clerodendrum phlomidis using HPTLC. Med. Chem. Res. 2014, 23, 1654–1660. [Google Scholar] [CrossRef]
  31. Yadav, A.K.; Thakur, J.K.; Agrawal, J.; Saikia, D.; Pal, A.; Gupta, M.M. Bioactive chemical constituents from the root of Clerodendrum phlomidis. Med. Chem. Res. 2015, 24, 1112–1118. [Google Scholar] [CrossRef]
  32. Kim, H.J.; Woo, E.-R.; Shin, C.-G.; Hwang, D.J.; Park, H.; Lee, Y.S. HIV-1 integrase inhibitory phenylpropanoid glycosides from Clerodendron trichotomum. Arch. Pharm. Res. 2001, 24, 286–291. [Google Scholar] [CrossRef] [PubMed]
  33. Kang, D.G.; Lee, Y.S.; Kim, H.J.; Lee, Y.M.; Lee, H.S. Angiotensin converting enzyme inhibitory phenylpropanoid glycosides from Clerodendron trichotomum. J. Ethnopharmacol. 2003, 89, 151–154. [Google Scholar] [CrossRef] [PubMed]
  34. Lee, J.-W.; Bae, J.J.; Kwak, J.H. Glycosides from the flower of Clerodendrum trichotomum. Korean J. Pharmacogn. 2016, 47, 301–306. [Google Scholar]
  35. Miyase, T.; Koizumi, A.; Ueno, A.; Noro, T.; Kuroyanagi, M.; Fukushima, S.; Akiyama, Y.; Takemoto, T. Studies on the acyl glycosides from Leucosceptrum japonicum (Miq.) Kitamura et Murata. Chem. Pharm. Bull. 1982, 30, 2732–2737. [Google Scholar] [CrossRef]
  36. Murata, T.; Arai, Y.; Miyase, T.; Yoshizaki, F. An alkaloidal glycoside and other constituents from Leucosceptrum japonicum. J. Nat. Med. 2009, 63, 402–407. [Google Scholar] [CrossRef]
  37. Olennikov, D.N. Synanthropic plants as an underestimated source of bioactive phytochemicals: A case of Galeopsis bifida (Lamiaceae). Plants 2020, 9, 1555. [Google Scholar] [CrossRef]
  38. Zhang, J.; Huang, Z.; Huo, H.-X.; Li, Y.-T.; Pang, D.-R.; Zheng, J.; Zhang, Q.; Zhao, Y.-F.; Tu, P.-F.; Li, J. Chemical constituents from Lagopsis supina (Steph.) Ik.-Gal. ex Knorr. Biochem. Syst. Ecol. 2015, 61, 424–428. [Google Scholar] [CrossRef]
  39. Yang, L.; He, J. Lagopsis supina extract and its fractions exert prophylactic effects against blood stasis in rats via anti-coagulation, anti-platelet activation and anti-fibrinolysis and chemical characterization by UHPLC-qTOF-MS/MS. Biomed. Pharmacother. 2020, 132, 110899. [Google Scholar] [CrossRef]
  40. He, J.; Yang, L. Diuretic effect of Lagopsis supina fraction in saline-loaded rats is mediated through inhibition of aquaporin and renin-angiotensin-aldosterone systems and up-regulation of atriopeptin. Biomed. Pharmacother. 2021, 139, 111554. [Google Scholar] [CrossRef]
  41. Olennikov, D.N.; Chirikova, N.K. Caffeoylglucaric acids and other phenylpropanoids from Siberian Leonurus species. Chem. Nat. Compd. 2016, 52, 915–917. [Google Scholar] [CrossRef]
  42. Tasdemir, D.; Scapozza, L.; Zerbe, O.; Linden, A.; Calis, I.; Sticher, O. Iridoid glycosides of Leonurus persicus. J. Nat. Prod. 1999, 62, 811–816. [Google Scholar] [CrossRef] [PubMed]
  43. Schmidt, S.; Jakab, M.; Jav, S.; Streif, D.; Pitschmann, A.; Zehl, M.; Purevsuren, M.; Glasl, S.; Ritter, M. Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells. J. Ethnopharmacol. 2013, 150, 85–94. [Google Scholar] [CrossRef] [PubMed]
  44. Pitschmann, A.; Zehl, M.; Heiss, E.; Purevsuren, S.; Urban, E.; Dirsch, M.V.; Glasl, S. Quantitation of phenylpropanoids and iridoids in insulin-sensitising extracts of Leonurus sibiricus L. (Lamiaceae). Phytochem. Anal. 2015, 27, 23–31. [Google Scholar] [CrossRef] [PubMed]
  45. Çaliş, I.; Hosny, M.; Khalifa, T.; Rüedi, P. Phenylpropanoid glycosides from Marrubium alysson. Phytochemistry 1992, 31, 3624–3626. [Google Scholar]
  46. Argyropoulou, A.; Samara, P.; Tsitsilonis, O.; Skaltsa, H. Polar constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their cytotoxic/cytostatic activity. Phytother. Res. 2012, 26, 1800–1806. [Google Scholar]
  47. Karioti, A.; Skaltsa, H.; Heilmann, J.; Sticher, O. Acylated flavonoid and phenylethanoid glycosides from Marrubium velutinum. Phytochemistry 2003, 64, 655–660. [Google Scholar] [CrossRef]
  48. Masoodi, M.; Ali, Z.; Liang, S.; Yin, H.; Wang, W.; Khan, I.A. Labdane diterpenoids from Marrubium vulgare. Phytochem. Lett. 2015, 13, 275–279. [Google Scholar] [CrossRef]
  49. Saracoglu, I.; Inoue, M.; Çalis, I.; Ogihara, Y. Studies on constituents with cytotoxic and cytostatic activity of two Turkish medicinal plants Plomis armeniaca and Scutellaria salviifolia. Biol. Pharm. Bull. 1995, 18, 1396–1400. [Google Scholar] [CrossRef]
  50. Kırmızıbekmez, H.; Montoro, P.; Piacente, S.; Pizza, C.; Dönmez, A.; Çalıs, I. Identification by HPLC-PAD-MS and quantification by HPLC-PAD of phenylethanoid glycosides of five Phlomis species. Phytochem. Anal. 2005, 16, 1–6. [Google Scholar] [CrossRef]
  51. Ersöz, T.; Saracoğlu, I.; Kırmızıbekmez, H.; Yalçın, F.N.; Harput, Ü.S.; Dönmez, A.A.; Çalıs, I. Iridoid, phenylethanoid and phenol glycosides from Phlomis chimerae. Hacet. Univ. J. Fac. Pharm. 2001, 21, 23–33. [Google Scholar]
  52. Stojković, D.; Gašić, U.; Drakulić, D.; Zengin, G.; Stevanović, M.; Rajčević, N.; Soković, M. Chemical profiling, antimicrobial, anti-enzymatic, and cytotoxic properties of Phlomis fruticosa L. J. Pharm. Biomed. Anal. 2021, 195, 113884. [Google Scholar] [CrossRef] [PubMed]
  53. Saracoglu, I.; Varel, M.; Çalıs, I.; Dönmez, A.A. Neolignan, flavonoid, phenylethanoid and iridoid glycosides from Phlomis integrifolia. Turk. J. Chem. 2003, 27, 739–747. [Google Scholar]
  54. Harput, U.S.; Çalıs, I.; Saracoglu, I.; Dönmez, A.A.; Nagatsu, A. Secondary metabolites from Phlomis syriaca and their antioxidant activities. Turk. J. Chem. 2006, 30, 383–390. [Google Scholar]
  55. Ersöz, T.; Schühly, W.; Popov, S.; Handjieva, N.; Sticher, O.; Çalıs, I. Iridoid and phenylethanoid glycosides from Phlomis longifolia var. longifolia. Nat. Prod. Lett. 2001, 15, 345–351. [Google Scholar] [CrossRef]
  56. Kırmızıbekmez, H.; Piacente, S.; Pizza, C.; Dönmez, A.A.; Çalıs, I. Iridoid and phenylethanoid glycosides from Phlomis nissolii and P. capitata. Z. Naturforsch. B 2004, 59, 609–613. [Google Scholar] [CrossRef]
  57. Çaliş, I.; Bedir, E.; Kirmizibekmez, H.; Ersöz, T.; Dönmez, A.A.; Khan, I.A. Secondary metabolites from Phlomis oppositiflora. Nat. Prod. Res. 2005, 19, 493–501. [Google Scholar] [CrossRef]
  58. Ersöz, T.; Alipieva, K.I.; Yalçın, F.N.; Akbay, P.; Handjieva, N.; Dönmez, A.A.; Popov, S.; Çaliş, I. Physocalycoside, a new phenylethanoid glycoside from Phlomis physocalyx Hub.-Mor. Z. Naturforsch. C 2003, 58, 471–476. [Google Scholar] [CrossRef]
  59. Ersöz, T.; Harput, U.S.; Çaliş, I.; Dönmez, A.A. Iridoid, phenylethanoid and monoterpene glycosides from Phlomis sieheana. Turk. J. Chem. 2002, 26, 1–8. [Google Scholar]
  60. Çaliş, I.; Kırmızıbekmez, H.; Beutler, J.A.; Dönmez, A.A.; Yalçın, F.N.; Kilic, E.; Özalp, M.; Rüedi, P.; Tasdemir, D. Secondary metabolites of Phlomis viscosa and their biological activities. Turk. J. Chem. 2005, 29, 71–81. [Google Scholar]
  61. Delazar, A.; Shoeb, M.; Kumarasamy, Y.; Byres, M.; Nahar, L.; Modarresi, M.; Sarker, S.D. Two bioactive ferulic acid derivatives from Eremostachys glabra. DARU J. Pharm. Sci. 2004, 12, 49–53. [Google Scholar]
  62. Çaliş, I.; Guevenc, A.; Armagan, M.; Koyuncu, M.; Gotfredsen, C.H.; Jensen, S.R. Secondary metabolites from Eremostachys laciniata. Nat. Prod. Commun. 2008, 3, 117–124. [Google Scholar] [CrossRef]
  63. Wang, J.; Gao, Y.-L.; Chen, Y.-L.; Chen, Y.-W.; Zhang, Y.; Xiang, L.; Pan, Z. Lamiophlomis rotata identification via ITS2 barcode and quality evaluation by UPLC-QTOF-MS coupled with multivariate analyses. Molecules 2018, 23, 3289. [Google Scholar] [PubMed]
  64. Li, T.; Jia, L.; Du, R.; Liu, C.; Huang, S.; Lu, H.; Han, L.; Chen, X.; Wang, Y.; Jiang, M. Comparative investigation of aerial part and root in Lamiophlomis rotata using UPLC-Q-Orbitrap-MS coupled with chemometrics. Arab. J. Chem. 2022, 15, 103740. [Google Scholar] [CrossRef]
  65. Çaliş, I.; Kırmızıbekmez, H.; Ersöz, T.; Dönmez, A.A.; Gotfredsen, C.H.; Jensen, S.R. Iridoid glucosides from Turkish Phlomis tuberosa. Z. Naturforsch. B 2005, 60, 1295–1298. [Google Scholar] [CrossRef]
  66. Wu, S.-J.; Chan, Y.-Y. Five new iridoids from roots of Salvia digitaloides. Molecules 2014, 19, 15521–15534. [Google Scholar] [CrossRef] [PubMed]
  67. Rungsimakan, S.; Rowan, M.G. Terpenoids, flavonoids and caffeic acid derivatives from Salvia viridis L. cvar. Blue Jeans. Phytochemistry 2014, 108, 177–188. [Google Scholar] [CrossRef]
  68. Grzegorczyk-Karolak, I.; Kiss, A.K. Determination of the phenolic profile and antioxidant properties of Salvia viridis L. shoots: A comparison of aqueous and hydroethanolic extracts. Molecules 2018, 23, 1468. [Google Scholar] [CrossRef]
  69. Zengin, G.; Mahomoodally, F.; Picot-Allain, C.; Diuzheva, A.; Jekőd, J.; Cziáky, Z.; Cvetanović, A.; Aktumsek, A.; Zeković, Z.; Rengasamy, K.R.R. Metabolomic profile of Salvia viridis L. root extracts using HPLC–MS/MS technique and their pharmacological properties: A comparative study. Ind. Crops Prod. 2019, 131, 266–280. [Google Scholar] [CrossRef]
  70. Xu, H.-T.; Zhang, C.-G.; He, Y.-Q.; Shi, S.-S.; Wang, Y.-L.; Chou, G.-X. Phenylethanoid glycosides from the Schnabelia nepetifolia (Benth.) P.D.Cantino promote the proliferation of osteoblasts. Phytochemistry 2019, 164, 111–121. [Google Scholar] [CrossRef]
  71. Matsa, M.; Bardakci, H.; Gousiadou, C.; Kirmizibekmez, H.; Skaltsa, H. Secondary metabolites from Scutellaria albida L. ssp. velenovskyi (Rech. f.) Greuter & Burdet. Biochem. Syst. Ecol. 2019, 83, 71–76. [Google Scholar]
  72. Olennikov, D.N.; Chirikova, N.K.; Tankhaeva, L.M. Phenolic compounds of Scutellaria baicalensis Georgi. Russ. J. Bioorg. Chem. 2010, 36, 816–824. [Google Scholar] [CrossRef]
  73. Qiao, X.; Li, R.; Song, W.; Miao, W.-J.; Liu, J.; Chen, H.-B.; Guo, D.; Ye, M. A targeted strategy to analyze untargeted mass spectral data: Rapid chemical profiling of Scutellaria baicalensis using ultra-highperformance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering. J. Chromatogr. A 2016, 1441, 83–95. [Google Scholar] [CrossRef] [PubMed]
  74. Yang, Z.-W.; Xu, F.; Liu, X.; Cao, Y.; Tang, Q.; Chen, Q.-Y.; Shang, M.-Y.; Liu, G.-X.; Wang, X.; Cai, S.-Q. An untargeted metabolomics approach to determine component differences and variation in their in vivo distribution between Kuqin and Ziqin, two commercial specifications of Scutellaria Radix. RSC Adv. 2017, 7, 54682–54695. [Google Scholar] [CrossRef]
  75. Zhang, F.; Li, Z.; Li, M.; Yuan, Y.; Cui, S.; Chen, J.; Li, R. An integrated strategy for profiling the chemical components of Scutellariae Radix and their exogenous substances in rats by ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2020, 34, e8823. [Google Scholar] [CrossRef]
  76. Shah, M.; Rahman, H.; Khan, A.; Bibi, S.; Ullah, O.; Ullah, S.; Ur Rehman, N.; Murad, W.; Al-Harrasi, A. Identification of α-glucosidase inhibitors from Scutellaria edelbergii: ESI-LC-MS and computational approach. Molecules 2022, 27, 1322. [Google Scholar] [CrossRef]
  77. Kuroda, M.; Iwabuchi, K.; Mimaki, Y. Chemical constituents of the aerial parts of Scutellaria lateriflora and their α-glucosidase inhibitory activities. Nat. Prod. Commun. 2012, 7, 471–474. [Google Scholar] [CrossRef]
  78. Çaliş, I.; Saracoğlu, I.; Başaran, A.A.; Sticher, O. Two phenethyl alcohol glycosides from Scutellaria orientalis subsp. pinnatifida. Phytochemistry 1993, 32, 1621–1623. [Google Scholar] [CrossRef]
  79. Kikuchi, Y.; Miyaichi, Y.; Yamaguchi, Y.; Kizu, H.; Tomimori, T. Studies on the Nepalese crude drugs. XII. On the phenolic compounds from the root of Scutellaria prostrata Jacq. ex Benth. Chem. Pharm. Bull. 1991, 39, 1047–1050. [Google Scholar] [CrossRef][Green Version]
  80. Lytra, K.; Tomou, E.-M.; Chrysargyris, A.; Drouza, C.; Skaltsa, H.; Tzortzakis, N. Traditionally used Sideritis cypria Post.: Phytochemistry, nutritional content, bioactive compounds of cultivated populations. Front. Pharmacol. 2020, 11, 650. [Google Scholar] [CrossRef]
  81. Lytra, K.; Tomou, E.-M.; Chrysargyris, A.; Christofi, M.-D.; Miltiadous, P.; Tzortzakis, N.; Skaltsa, H. Bio-guided investigation of Sideritis cypria methanol extract driven by in vitro antioxidant and cytotoxic assays. Chem. Biodivers. 2021, 18, e2000966. [Google Scholar] [CrossRef]
  82. Tomou, E.-M.; Chatzopoulou, P.; Skaltsa, H. NMR analysis of cultivated Sideritis euboea Heldr. Phytochem. Anal. 2020, 31, 147–153. [Google Scholar] [CrossRef] [PubMed]
  83. Tomou, E.-M.; Papaemmanouil, C.D.; Diamantis, D.A.; Kostagianni, A.D.; Chatzopoulou, P.; Mavromoustakos, T.; Tzakos, A.G.; Skaltsa, H. Anti-ageing potential of S. euboea Heldr. phenolics. Molecules 2021, 26, 3151. [Google Scholar] [CrossRef] [PubMed]
  84. Akcos, Y.; Ezer, N.; Çalis, I.; Demirdamar, R.; Tel, B.C. Polyphenolic Compounds of Sideritis lycia and their anti-inflammatory activity. Pharm. Biol. 1999, 37, 118–122. [Google Scholar] [CrossRef]
  85. Şahin, F.P.; Ezer, N.; Çalış, I. Three acylated flavone glycosides from Sideritis ozturkii Aytac & Aksoy. Phytochemistry 2004, 65, 2095–2099. [Google Scholar] [PubMed]
  86. Charami, M.-T.; Lazari, D.; Karioti, A.; Skaltsa, H.; Hadjipavlou-Litina, D.; Souleles, C. Antioxidant and antiinflammatory activities of Sideritis perfoliata subsp. perfoliata (Lamiaceae). Phytother. Res. 2008, 22, 450–454. [Google Scholar] [CrossRef]
  87. Petreska, J.; Stefkov, G.; Kulevanova, S.; Alipieva, K.; Bankova, V.; Stefova, M. Phenolic compounds of mountain tea from the Balkans: LC/DAD/ESI/MSn profile and content. Nat. Prod. Commun. 2011, 6, 21–30. [Google Scholar] [CrossRef]
  88. Pljevljakušić, D.; Šavikin, K.; Janković, K.; Zdunić, G.; Ristić, M.; Godjevac, D.; Konić-Ristić, A. Chemical properties of the cultivated Sideritis raeseri Boiss. & Heldr. subsp. raeseri. Food Chem. 2011, 124, 226–233. [Google Scholar]
  89. Menković, N.; Gođevac, D.; Šavikin, K.; Zdunić, G.; Milosavljević, S.; Bojadži, A.; Avramoski, O. Bioactive compounds of endemic species Sideritis raeseri subsp. raeseri grown in National Park Galičica. Rec. Nat. Prod. 2013, 7, 161–168. [Google Scholar]
  90. Kokras, N.; Poulogiannopoulou, E.; Sotiropoulos, M.G.; Paravatou, R.; Goudani, E.; Dimitriadou, M.; Papakonstantinou, E.; Doxastakis, G.; Perrea, D.N.; Hloupis, G.; et al. Behavioral and neurochemical effects of extra virgin olive oil total phenolic content and Sideritis extract in female mice. Molecules 2020, 25, 5000. [Google Scholar] [CrossRef]
  91. Tomou, E.-M.; Lytra, K.; Chrysargyris, A.; Christofi, M.-D.; Miltiadous, P.; Corongiu, G.L.; Tziouvelis, M.; Tzortzakis, N.; Skaltsa, H. Polar constituents, biological effects and nutritional value of Sideritis sipylea Boiss. Nat. Prod. Res. 2022, 36, 4200–4204. [Google Scholar] [CrossRef]
  92. Miyase, T.; Ueno, A.; Kitani, T.; Kobayashi, H.; Kawahara, Y.; Yamahara, J. Studies on Stachys sieboldii Miq. I. Isolation and structures of new glycosides. J. Pharm. Soc. Jpn. 1990, 110, 652–657. [Google Scholar] [CrossRef] [PubMed]
  93. Nishimura, H.; Sasaki, H.; Inagaki, N.; Chin, M.; Mitsuhashi, H. Nine phenylethyl alcohol glycosides from Stachys sieboldii. Phytochemistry 1991, 30, 965–969. [Google Scholar] [CrossRef]
  94. Venditti, A.; Frezza, C.; Celona, D.; Bianco, A.; Serafini, M.; Cianfaglione, K.; Fiorini, D.; Ferraro, S.; Maggi, F.; Lizzi, A.R.; et al. Polar constituents, protection against reactive oxygen species, and nutritional value of Chinese artichoke (Stachys affinis Bunge). Food Chem. 2017, 221, 473–481. [Google Scholar] [CrossRef]
  95. Pritsas, A.; Tomou, E.-M.; Tsitsigianni, E.; Papaemmanouil, C.D.; Diamantis, D.A.; Chatzopoulou, P.; Tzakos, A.G.; Skaltsa, H. Valorisation of stachysetin from cultivated Stachys iva Griseb. as anti-diabetic agent: A multi-spectroscopic and molecular docking approach. J. Biomol. Struct. Dyn. 2020, 39, 6452–6466. [Google Scholar] [CrossRef] [PubMed]
  96. Delazar, A.; Delnavazi, M.R.; Nahar, L.; Moghadam, S.B.; Mojara, M.; Gupta, A.; Williams, A.S.; Rahman, M.M.; Sarker, S.D. Lavandulifolioside B: A new phenylethanoid glycoside from the aerial parts of Stachys lavandulifolia Vahl. Nat. Prod. Res. 2011, 25, 8–16. [Google Scholar] [CrossRef]
  97. Ergun, B.; Goger, F.; Kose, Y.B.; Iscan, G. Determination of phenolic compounds of Stachys rupestris Montbret et Aucher ex Bentham by LC-MS/MS and its biological activities. Fresenius Environ. Bull. 2018, 27, 1176–1182. [Google Scholar]
  98. Afouxenidi, A.; Milošević-Ifantis, T.; Skaltsa, H. Secondary metabolites from Stachys tetragona Boiss. & Heldr. ex Boiss. and their chemotaxonomic significance. Biochem. Syst. Ecol. 2018, 81, 83–85. [Google Scholar]
  99. Kanchanapoom, T.; Kasai, R.; Chumsri, P.; Hiraga, Y.; Yamasaki, K. Megastigmane and iridoid glucosides from Clerodendrum inerme. Phytochemistry 2001, 58, 333–336. [Google Scholar] [CrossRef]
  100. Passon, M.; Weber, F.; Jung, N.U.; Bartels, D. Profiling of phenolic compounds in desiccation-tolerant and non-desiccation-tolerant Linderniaceae. Phytochem. Anal. 2021, 32, 521–529. [Google Scholar] [CrossRef] [PubMed]
  101. Bai, H.; Li, S.; Yin, F.; Hu, L. Isoprenylated naphthoquinone dimers firmianones A, B, and C from Firmiana platanifolia. J. Nat. Prod. 2005, 68, 1159–1163. [Google Scholar] [CrossRef]
  102. Wu, L.; Liu, J.; Huang, W.; Wang, Y.; Chen, Q.; Lu, B. Exploration of Osmanthus fragrans Lour.’s composition, nutraceutical functions and applications. Food Chem. 2022, 377, 131853. [Google Scholar] [CrossRef]
  103. Shi, R.; Zhang, C.; Gong, X.; Yang, M.; Ji, M.; Jiang, L.; Leonti, M.; Yao, R.; Li, M. The genus Orobanche as food and medicine: An ethnopharmacological review. J. Ethnopharmacol. 2020, 263, 113154. [Google Scholar] [CrossRef]
  104. Jedrejek, D.; Pawelec, S.; Piwowarczyk, R.; Pecio, Ł.; Stochmal, A. Identification and occurrence of phenylethanoid and iridoid glycosides in six Polish broomrapes (Orobanche spp. and Phelipanche spp., Orobanchaceae). Phytochemistry 2020, 170, 112189. [Google Scholar] [CrossRef]
  105. Yang, M.-Z.; Wang, X.-Q.; Li, C. Chemical constituents from Orobanche cernua. Chin. Tradit. Herb. Drugs 2014, 45, 2447–2452. [Google Scholar]
  106. Qu, Z.-Y.; Zhang, Y.-W.; Yao, C.-L.; Jin, Y.-P.; Zheng, P.-H.; Sun, C.-H.; Liu, J.-X.; Wang, Y.-S.; Wang, Y.-P. Chemical constituents from Orobanche cernua Loefling. Biochem. Syst. Ecol. 2015, 60, 199–203. [Google Scholar] [CrossRef]
  107. Wang, X.; Li, C.; Jiang, L.; Huang, H.; Li, M. Phenylethaniod glycosides from Orobanche pycnostachya Hance and their chemotaxonomic significance. Biochem. Syst. Ecol. 2020, 93, 104168. [Google Scholar] [CrossRef]
  108. Ersöz, T.; Berkman, M.Z.; Taşdemir, D.; Çaliş, I.; Ireland, C.M. Iridoid and phenylethanoid glycosides from Euphrasia pectinata. Turk. J. Chem. 2002, 26, 179–188. [Google Scholar]
  109. Ersöz, T.; Berkman, M.Z.; Taşdemir, D.; Ireland, C.M.; Çaliş, I. An iridoid glucoside from Euphrasia pectinata. J. Nat. Prod. 2000, 63, 1449–1450. [Google Scholar] [CrossRef]
  110. Akdemir, Z.; Çaliş, I. Iridoid and phenylpropanoid glycosides from Pedicularis comosa var. acmodonta Boiss. Doga Turk. J. Pharm. 1992, 2, 63–70. [Google Scholar]
  111. Gao, J.J.; Jia, Z.J. Lignan: Iridoid and phenylpropanoid glycosides from Pedicularis alaschanica. Ind. J. Chem. Sect. B-Org. Chem. Incl. Med. Chem. 1995, 34, 466–468. [Google Scholar]
  112. Wang, P.; Kung, J.; Zheng, R.; Yung, Z.; Lu, J.; Guo, J.; Jiu, Z. Scavenging effects of phenylpropanoid glycosides from Pedicularis on superoxide anion and hydroxyl radical by the spin trapping method (95)02255-4. Biochem. Pharmacol. 1996, 51, 687–691. [Google Scholar] [CrossRef] [PubMed]
  113. Yin, J.-G.; Yuan, C.-S.; Jia, Z.-J. A new iridoid and other chemical constituents from Pedicularis kansuensis forma albiflora Li. Arch. Pharm. Res. 2007, 30, 431–435. [Google Scholar] [CrossRef] [PubMed]
  114. Chu, H.B.; Tan, N.H.; Xiong, J.; Zhang, Y.M.; Ji, C.J. Chemical constituents of Pedicularis dolichocymba Hand.-Mazz. Nat. Prod. Res. Dev. 2007, 19, 584–587. [Google Scholar]
  115. Ma, S.; Yang, A.; Yang, L.; Guo, W.; Li, C.; Shang, Q. Chemical constituents of Pedicularis kansuensis. Chem. Nat. Compd. 2017, 53, 586–588. [Google Scholar] [CrossRef]
  116. Venditti, A.; Frezza, C.; Serafini, M.; Bianco, A. Iridoids and phenylethanoid from Pedicularis kerneri Dalla Torre growing in Dolomites, Italy. Nat. Prod. Res. 2016, 30, 327–331. [Google Scholar] [CrossRef] [PubMed]
  117. Lan, Y.; Chi, X.; Zhou, G.; Zhao, X. Antioxidants from Pedicularis longiflora var. tubiformis (Klotzsch) P. C. Tsoong. Rec. Nat. Prod. 2018, 12, 332–339. [Google Scholar] [CrossRef]
  118. Akdemir, Z.; Çaliş, I.; Junior, P. Iridoids and phenyipropanoid glycosides from Pedicularis nordmanniana. Planta Med. 1991, 57, 584–585. [Google Scholar] [CrossRef]
  119. Wang, Y.; Shao, M.-H.; Yuan, S.-W.; Lu, Y.; Wang, Q. A new monoterpene glycoside from Pedicularis verticillata and anticomplementary activity of its compounds. Nat. Prod. Res. 2021, 35, 1–8. [Google Scholar] [CrossRef]
  120. Takeda, Y. A new phenolic glycoside from Phtheirospermum japonicum. J. Nat. Prod. 1988, 51, 180–183. [Google Scholar] [CrossRef]
  121. Friščić, M.; Bucar, F.; Hazler Pilepić, K. LC-PDA-ESI-MSn analysis of phenolic and iridoid compounds from Globularia spp. J. Mass Spectrom. 2016, 51, 1211–1236. [Google Scholar] [CrossRef]
  122. Friščić, M.; Petlevski, R.; Kosalec, I.; Madunić, J.; Matulić, M.; Bucar, F.; Hazler Pilepić, K.; Maleš, Ž. Globularia alypum L. and related species: LC-MS profiles and antidiabetic, antioxidant, anti-inflammatory, antibacterial and anticancer potential. Pharmaceuticals 2022, 15, 506. [Google Scholar] [CrossRef] [PubMed]
  123. Kirmizibekmez, H.; Çaliş, I.; Piacente, S.; Pizza, C. Phenolic compounds from Globularia cordifolia. Turk. J. Chem. 2004, 28, 455–460. [Google Scholar]
  124. Çaliş, I.; Kirmizibekmez, H.; Taşdemir, D.; Ireland, C.M. Iridoid glycosides from Globularia davisiana. Chem. Pharm. Bull. 2002, 50, 678–680. [Google Scholar] [CrossRef] [PubMed]
  125. Çaliş, I.; Kirmizibekmez, H.; Taşdemir, D.; Sticher, O.; Ireland, C.M. Sugar esters from Globularia orientalis. Z. Naturforsch. C 2002, 57, 591–596. [Google Scholar] [CrossRef] [PubMed]
  126. Kirmizibekmez, H.; Çaliş, I.; Piacente, S.; Pizza, C. Iridoid and phenylethyl glycosides from Globularia sintenisii. Helv. Chim. Acta 2004, 87, 1172–1179. [Google Scholar] [CrossRef]
  127. Li, C.; Liu, Y.; Abdulla, R.; Aisa, H.A.; Suo, Y. Determination of phenylethanoid glycosides in Lagotis brevituba Maxim. by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Anal. Lett. 2014, 47, 1862–1873. [Google Scholar] [CrossRef]
  128. Yang, A.-M.; Lu, R.-H.; Shi, Y.-P. Phenylpropanoids from Lagotis ramalana. Nat. Prod. Res. Dev. 2007, 19, 263–265. [Google Scholar]
  129. Ye, M.; Zhao, Y.; Norman, V.L.; Starks, C.M.; Rice, S.M.; Goering, M.G.; O’Neil-Johnson, M.; Eldridge, G.R.; Hu, J.-F. Antibiofilm phenylethanoid glycosides from Penstemon centranthifolius. Phytother. Res. 2010, 24, 778–781. [Google Scholar] [CrossRef]
  130. Ismail, L.D.; El-Azizi, M.M.; Khalifa, T.I.; Stermitz, F.R. Verbascoside derivatives and iridoid glycosides from Penstemon crandallii. Phytochemistry 1995, 39, 1391–1393. [Google Scholar] [CrossRef]
  131. Zhou, B.-N.; Bahler, B.D.; Hofmann, G.A.; Mattern, M.R.; Johnson, R.K.; Kingston, D.G.I. Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCr-inhibitory activity. J. Nat. Prod. 1998, 61, 1410–1412. [Google Scholar] [CrossRef]
  132. Miyase, T.; Ishino, M.; Akahori, C.; Ueno, A.; Ohkawa, Y.; Tanizawa, H. Phenylethanoid glycosides from Plantago asiatica. Phytochemistry 1991, 30, 2015–2018. [Google Scholar] [CrossRef]
  133. Qi, M.; Xiong, A.; Geng, F.; Yang, L.; Wang, Z. A novel strategy for target profiling analysis of bioactive phenylethanoid glycosides in Plantago medicinal plants using ultra-performance liquid chromatography coupled with tandem quadrupole mass spectrometry. J. Sep. Sci. 2012, 35, 1470–1478. [Google Scholar] [CrossRef] [PubMed]
  134. Wang, D.; Qi, M.; Yang, Q.; Tong, R.; Wang, R.; Annie Bligh, S.W.; Yang, L.; Wang, Z. Comprehensive metabolite profiling of Plantaginis Semen using ultra high-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry coupled with elevated energy technique. J. Sep. Sci. 2016, 39, 1842–1852. [Google Scholar] [CrossRef]
  135. Mazzutti, S.; Salvador Ferreira, S.R.; Herrero, M.; Ibãnez, E. Intensified aqueous-based processes to obtain bioactive extracts from Plantago major and Plantago lanceolata. J. Supercrit. Fluids 2017, 119, 64–71. [Google Scholar] [CrossRef]
  136. Afifi, M.S.A.; Amer, M.M.A.; ZaghIoul, A.M.; Ahmad, M.M.; Kinghorn, A.D.; Zaghloul, M.G. Chemical constituents of Plantago squarrosa. Mansoura J. Pharm. Sci. 2001, 17, 65–84. [Google Scholar]
  137. Genc, Y.; Sohretoglu, D.; Harput, U.S.; Ishiuchi, K.; Makino, T.; Saracoglu, I. Chemical constituents of Plantago holosteum and evaluation of their chemotaxonomic significance. Chem. Nat. Compd. 2020, 56, 566–568. [Google Scholar] [CrossRef]
  138. Dereli, F.T.G.; Genc, Y.; Saracoglu, I.; Akkol, E.K. Enzyme inhibitory assessment of the isolated constituents from Plantago holosteum Scop. Z. Naturforsch. C 2020, 75, 121–128. [Google Scholar] [CrossRef]
  139. Sasaki, H.; Nishimura, H.; Chin, M.; Mitsuhashi, H. Hydroxycinnamic acid esters of phenylalcohol glycosides from Rehmannia glutinosa var. purpurea. Phytochemistry 1989, 28, 875–879. [Google Scholar] [CrossRef]
  140. Nishimura, H.; Morota, T.; Yamaguchi, T.; Chin, M. Extraction of Phenethyl Alcohol Derivatives as Aldose Reductase Inhibitors for Treatment of Diabetes-Related Diseases. Japan Kokai Tokkyo Koho Patent JP 02036189, 1990. p. 13. [Google Scholar]
  141. Anh, N.T.H.; Sung, T.V.; Franke, K.; Wessjohann, L.A. Phytochemical studies of Rehmannia glutinosa rhizomes. Pharmazie 2003, 58, 593–595. [Google Scholar]
  142. Li, X.; Zhou, M.; Shen, P.; Zhang, J.; Chu, C.; Ge, Z.; Yan, J. Chemical constituents form Rehmannia glutinosa. China J. Chin. Mater. Med. 2011, 36, 3125–3129. [Google Scholar]
  143. Li, M.-N.; Dong, X.; Gao, W.; Liu, X.-G.; Wang, R.; Li, P.; Yang, H. Global identification and quantitative analysis of chemical constituents in traditional Chinese medicinal formula Qi-Fu-Yin by ultra-high performance liquid chromatography coupled with mass spectrometry. J. Pharm. Biomed. Anal. 2015, 114, 376–389. [Google Scholar] [CrossRef] [PubMed]
  144. Song, Q.-Q. Establishment of HPLC fingerprint of Rehmanniae Radix and its HPLC-ESI-MS analysis. Chin. Tradit. Herb. Drugs 2016, 24, 4247–4252. [Google Scholar]
  145. Zhang, B.; Weston, P.A.; Gu, L.; Zhang, B.; Li, M.; Wang, F.; Tu, W.; Wang, J.; Weston, L.A.; Zhang, Z. Identification of phytotoxic metabolites released from Rehmannia glutinosa suggest their importance in the formation of its replant problem. Plant Soil 2019, 441, 439–454. [Google Scholar] [CrossRef]
  146. Thu, V.K.; Thoa, N.T.; Hien, N.T.T.; Hang, D.T.T.; Kiem, P.V. Iridoid glycosides link with phenylpropanoids from Rehmannia glutinosa. Nat. Prod. Res. 2022, in press. [Google Scholar] [CrossRef] [PubMed]
  147. Ochi, M.; Matsunami, K.; Otsuka, H.; Takeda, Y. A new iridoid glycoside and NO production inhibitory activity of compounds isolated from Russelia equisetiformis. J. Nat. Med. 2012, 66, 227–232. [Google Scholar] [CrossRef]
  148. Yamamoto, A.; Nitta, S.; Miyase, T.; Ueno, A.; Wu, L.-J. Phenylethanoid and lignan-iridoid complex glycosides from roots of Buddleja davidii. Phytochemistry 1993, 32, 421–425. [Google Scholar] [CrossRef]
  149. Lu, J.-H.; Pu, X.-P.; Li, Y.-Y.; Zhao, Y.-Y.; Tu, G.Z. Bioactive phenylethanoid glycosides from Buddleia lindleyana. Z. Naturforsch. B 2005, 60, 211–214. [Google Scholar] [CrossRef]
  150. Huang, F.-B.; Liang, N.; Hussain, N.; Zhou, X.-D.; Ismail, M.; Xie, Q.-L.; Yu, H.-H.; Jian, Y.-Q.; Peng, C.-Y.; Li, B.; et al. Anti-inflammatory and antioxidant activities of chemical constituents from the flower buds of Buddleja officinalis. Nat. Prod. Res. 2022, 36, 3031–3042. [Google Scholar] [CrossRef]
  151. Han, M.-F.; Zhang, X.; Zhang, L.-Q.; Li, Y.-M. Iridoid and phenylethanol glycosides from Scrophularia umbrosa with inhibitory activity on nitric oxide production. Phytochem. Lett. 2018, 28, 37–41. [Google Scholar] [CrossRef]
  152. Frezza, C.; Bianco, A.; Serafini, M.; Foddai, S.; Salustri, M.; Reverberi, M.; Gelardi, L.; Bonina, A.; Bonina, F.P. HPLC and NMR analysis of the phenyl-ethanoid glycosides pattern of Verbascum thapsus L. cultivated in the Etnean area. Nat. Prod. Res. 2019, 33, 1310–1316. [Google Scholar] [CrossRef]
  153. de la Luz Cádiz-Gurrea, M.; Olivares-Vicente, M.; Herranz-López, M.; Arraez-Roman, D.; Fernández-Arroyo, S.; Micol, V.; Segura-Carretero, A. Bioassay-guided purification of Lippia citriodora polyphenols with AMPK modulatory activity. J. Funct. Foods 2018, 46, 514–520. [Google Scholar] [CrossRef]
  154. Ono, M.; Oda, E.; Tanaka, T.; Iida, Y.; Yamasaki, T.; Masuoka, C.; Ikeda, T.; Nohara, T. DPPH radical-scavenging effect on some constituents from the aerial parts of Lippia triphylla. J. Nat. Med. 2008, 62, 101–106. [Google Scholar] [CrossRef]
  155. Olivares-Vicente, M.; Sánchez-Marzo, N.; Encinar, J.A.; De la Luz Cádiz-Gurrea, M.; Lozano-Sánchez, J.; Segura-Carretero, A.; Arraez-Roman, D.; Riva, C.; Barrajón-Catalán, E.; Herranz-López, M.; et al. The potential synergistic modulation of AMPK by Lippia citriodora compounds as a target in metabolic disorders. Nutrients 2019, 11, 2961. [Google Scholar] [CrossRef]
  156. Sánchez-Marzo, N.; Lozano-Sánchez, J.; De la Luz Cádiz-Gurrea, M.; Herranz-López, M.; Micol, V.; Segura-Carretero, A. Relationships between chemical structure and antioxidant activity of isolated phytocompounds from Lemon Verbena. Antioxidants 2019, 8, 324. [Google Scholar] [CrossRef]
  157. Saidi, I.; Waffo-Teguo, P.; Ayeb-Zakhama, A.E.L.; Harzallah-Skhiri, F.; Marchal, A.; Jannet, H.B. Phytochemical study of the trunk bark of Citharexylum spinosum L. growing in Tunisia: Isolation and structure elucidation of iridoid glycosides. Phytochemistry 2018, 146, 47–55. [Google Scholar] [CrossRef]
  158. Timóteo, P.; Karioti, A.; Leitão, S.G.; Vincieri, F.F.; Bilia, A.R. A validated HPLC method for the analysis of herbal teas from three chemotypes of Brazilian Lippia alba. Food Chem. 2015, 175, 366–373. [Google Scholar] [CrossRef]
  159. Abe, F.; Nagao, T.; Okabe, H. Antiproliferative constituents in plants 9.1) Aerial parts of Lippia dulcis and Lippia canescens. Biol. Pharm. Bull. 2002, 25, 920–922. [Google Scholar] [CrossRef]
  160. Froelich, S.; Gupta, M.P.; Siems, K.; Jenett-Siems, K. Phenylethanoid glycosides from Stachytarpheta cayennensis (Rich.) Vahl, Verbenaceae, a traditional antimalarial medicinal plant. Braz. J. Pharmacogn. 2008, 18, 517–520. [Google Scholar] [CrossRef]
  161. Toledo de Silva, M.V.; Garrett, R.; Simas, D.L.R.; Ungaretti Paleo Konno, T.; Frazão Muzitano, M.; Corrêa Pinto, S.; Barth, T. Chemical profile of Stachytarpheta schottiana by LC-HRMS/MS dereplication and molecular networking. Rodriguésia 2021, 72, 1–11. [Google Scholar]
  162. Ono, M.; Oishi, K.; Abe, H.; Masuoka, C.; Okawa, M.; Ikeda, T.; Nohara, T. New iridoid glucosides from the aerial parts of Verbena brasiliensis. Chem. Pharm. Bull. 2006, 54, 1421–1424. [Google Scholar] [CrossRef] [PubMed]
  163. Yokosuka, A.; Honda, M.; Kondo, H.; Mimaki, Y. Chemical constituents of the whole plant of Verbena hastata and their inhibitory activity against the production of AGEs. Nat. Prod. Commun. 2021, 16, 1–5. [Google Scholar] [CrossRef]
  164. Martin, F.; Hay, A.-E.; Corno, L.; Gupta, M.P.; Hostettmann, K. Iridoid glycosides from the stems of Pithecoctenium crucigerum (Bignoniaceae). Phytochemistry 2007, 68, 1307–1311. [Google Scholar] [CrossRef] [PubMed]
  165. Yang, Z.-Y.; Yuan, H.; Zhou, Y.; Lin, C.-Z.; Peng, G.-T.; Wu, A.-Z.; Zhu, C.-C. Phenylpropanoid compounds isolated from Callicarpa kwangtungensis and antibacterial activity research. Nat. Prod. Res. Dev. 2019, 31, 1928–1933. [Google Scholar]
  166. Niu, C.; Li, Q.; Yang, L.-P.; Zhang, Z.-Z.; Zhang, W.-K.; Liu, Z.-Q.; Wang, J.-H.; Wang, Z.-H.; Wang, H. Phenylethanoid glycosides from Callicarpa macrophylla Vahl. Phytochem. Lett. 2020, 38, 65–69. [Google Scholar] [CrossRef]
  167. Khitri, W.; Smati, D.; Mitaine-Offer, A.-C.; Paululat, T.; Lacaille-Dubois, M.-A. Chemical constituents from Phlomis bovei Noë and their chemotaxonomic significance. Biochem. Syst. Ecol. 2020, 91, 104054. [Google Scholar] [CrossRef]
  168. Saracoglu, I.; Harput, U.S.; Kojima, K.; Ogihara, Y. Iridoid and phenylpropanoid glycosides from Phlomis pungens var. pungens. Hacet. Univ. J. Fac. Pharm. 1997, 17, 63–72. [Google Scholar]
  169. Saracoglu, I.; Kojima, K.; Harput, U.S.; Ogihara, Y. Anew phenylethanoid glycoside from Phlomis pungens Willd. var. pungens. Chem. Pharm. Bull. 1998, 46, 726–727. [Google Scholar] [CrossRef]
  170. Saracoglu, I.; Suleimanov, T.; Shukurova, A.; Dogan, Z. Iridoids and phenylethanoid glycosides from Phlomis pungens of the flora of Azerbaijan. Chem. Nat. Compd. 2017, 53, 576–579. [Google Scholar] [CrossRef]
  171. Harput, U.S.; Saracoglu, I.; Çaliş, I.; Dönmez, A.A.; Nagatsu, A. Secondary Metabolites from Phlomis kotschyana. Turk. J. Chem. 2004, 28, 767–774. [Google Scholar]
  172. Bader, A.; Tuccinardi, T.; Granchi, C.; Martinelli, A.; Macchia, M.; Minutolo, F.; De Tommasi, N.; Braca, A. Phenylpropanoids and flavonoids from Phlomis kurdica as inhibitors of human lactate dehydrogenase. Phytochemistry 2015, 116, 262–268. [Google Scholar] [CrossRef]
  173. Saracoglu, I.; Harput, U.S.; Çaliş, I.; Ogihara, Y. Phenolic constituents from Phlomis lycia. Turk. J. Chem. 2002, 26, 133–142. [Google Scholar]
  174. Yue, H.-L.; Zhao, X.-H.; Mei, L.-J.; Shao, Y. Separation and purification of five phenylpropanoid glycosides from Lamiophlomis rotata (Benth.) Kudo by a macroporous resin column combined with high-speed counter-current chromatography. J. Sep. Sci. 2013, 36, 3123–3129. [Google Scholar] [CrossRef] [PubMed]
  175. Nguyen, D.H.; Le, D.D.; Zhao, B.T.; Ma, E.S.; Min, B.S.; Woo, M.H. Antioxidant compounds isolated from the roots of Phlomis umbrosa Turcz. Nat. Prod. Sci. 2018, 24, 119–124. [Google Scholar] [CrossRef]
  176. Dou, H.; Liao, X.; Peng, S.-L.; Pan, Y.-J.; Ding, L.S. Chemical constituents from the roots of Schnabelia tetradonta. Helv. Chim. Acta 2003, 86, 2797–2804. [Google Scholar] [CrossRef]
  177. Li, B.J.; Chen, C.-X.; Dou, H.; Li, R.; Ding, L.-S. Chemical constituents from the aerial parts of Schnabelia tetradonta. Nat. Prod. Res. Dev. 2006, 18, 61–64. [Google Scholar]
  178. Miyase, T.; Yamamoto, R.; Ueno, A. Phenylethanoid glycosides from Stachys officinalis. Phytochemistry 1996, 43, 475–479. [Google Scholar] [CrossRef] [PubMed]
  179. Georgiev, M.I.; Ali, K.; Alipieva, K.; Verpoorte, R.; Choi, Y.H. Metabolic differentiations and classification of Verbascum species by NMR-based metabolomics. Phytochemistry 2011, 72, 2045–2051. [Google Scholar] [CrossRef] [PubMed]
  180. Warashina, T.; Miyase, T.; Ueno, A. Phenylethanoid and lignan glycosides from Verbascum thapsus. Phytochemistry 1992, 31, 961–965. [Google Scholar] [CrossRef]
  181. Abou Gazar, H.; Bedir, E.; Khan, I.A.; Çaliş, I. Wiedemanniosides A-E: New phenylethanoid glycosides from the roots of Verbascum wiedemannianum. Planta Med. 2003, 69, 814–819. [Google Scholar]
  182. Georgiev, M.I.; Alipieva, K.; Orhna, I.; Abrashev, R.; Denev, P.; Angelova, M. Antioxidant and cholinesterase inhibitory activities of Verbascum xanthophoeniceum Griseb. and its phenylethanoid glycosides. Food Chem. 2011, 128, 100–105. [Google Scholar] [CrossRef]
  183. Dimitrova, P.; Kostadinova, E.; Milanova, V.; Alipieva, K.; Georgiev, M.I.; Ivanovska, N. Anti-inflammatory properties of extracts and compounds isolated from Verbascum xanthophoeniceum Griseb. Phytother. Res. 2012, 26, 1681–1687. [Google Scholar] [CrossRef] [PubMed]
  184. Abdel-Hady, H.; El-Sayed, M.M.; Abdel-Hady, A.A.; Hashash, M.M.; Abdel-Hady, A.M.; Aboushousha, T.; Abdel-Hameed, E.-S.S.; Abdel-Lateef, E.E.-S.; Morsi, E.A. Nephroprotective activity of methanolic extract of Lantana camara and squash (Cucurbita pepo) on cisplatin-induced nephrotoxicity in rats and identification of certain chemical constituents of Lantana camara by HPLC-ESI- MS. Pharmacogn. J. 2018, 10, 136–147. [Google Scholar] [CrossRef]
  185. Heilmann, J.; Çaliş, I.; Kirmizibekmez, H.; Schühly, W.; Harput, U.S.; Sticher, O. Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes: Structure-activity relationships. Planta Med. 2000, 66, 746–748. [Google Scholar] [CrossRef] [PubMed]
  186. Saidi, I.; Nimbarte, V.D.; Schwalbe, H.; Waffo-Téguo, P.; Harrathe, A.H.; Mansoure, L.; Alwasele, S.; Jannet, H.B. Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis. Bioorg. Chem. 2020, 102, 104093. [Google Scholar] [CrossRef] [PubMed]
  187. Li, P.; Qi, M.; Hu, H.; Liu, Q.; Yang, Q.; Wang, D.; Guo, F.; Bligh, S.W.A.; Wang, Z.; Yang, L. Structure-inhibition relationship of phenylethanoid glycosides on angiotensin-converting enzyme using ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. RSC Adv. 2015, 5, 51701–51707. [Google Scholar] [CrossRef]
  188. Karioti, A.; Protopappa, A.; Megoulas, N.; Skaltsa, H. Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. Bioorg. Med. Chem. 2007, 15, 2708–2714. [Google Scholar] [CrossRef]
  189. Li, Y.-Y.; Lu, J.-H.; Li, Q.; Zhao, Y.-Y.; Pu, X.-P. Pedicularioside A from Buddleia lindleyana inhibits cell death induced by 1-methyl-4-phenylpyridinium ions (MPP+) in primary cultures of rat mesencephalic neurons. Eur. J. Pharmacol. 2008, 579, 134–140. [Google Scholar] [CrossRef]
  190. Li, W.; Zheng, R.; Jia, Z.; Zou, Z.; Lin, N. Repair effect of phenylpropanoid glycosides on thymine radical anion induced by pulse radiolysis. Biophys. Chem. 1997, 67, 281–286. [Google Scholar] [CrossRef]
  191. Cespedes, C.L.; Muñoz, E.; Salazar, J.R.; Yamaguchi, L.; Werner, E.; Alarcon, J.; Kubo, I. Inhibition of cholinesterase activity by extracts, fractions and compounds from Calceolaria talcana and C. integrifolia (Calceolariaceae: Scrophulariaceae). Food Chem. Toxicol. 2013, 62, 919–926. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Article Metrics

Citations

Article Access Statistics

Journal Statistics
Multiple requests from the same IP address are counted as one view.
Download PDF
Identification of Bioactive Peptides from Nannochloropsis oculata Using a Combination of Enzymatic Treatment, in Silico Analysis and Chemical Synthesis
Previous
Different Extracellular β-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin
Next