Next Article in Journal
Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
Next Article in Special Issue
Assessment of Mechanisms Involved in Antinociception Produced by the Alkaloid Caulerpine
Previous Article in Journal
Structures of New Phenolics Isolated from Licorice, and the Effectiveness of Licorice Phenolics on Vancomycin-Resistant Enterococci
Previous Article in Special Issue
Preparative Isolation of Seven Diterpenoid Alkaloids from Aconitum coreanum by pH-Zone-Refining Counter-Current Chromatography
Article Menu

Export Article

Molecules 2014, 19(9), 13042-13060; doi:10.3390/molecules190913042

Review
Alkaloids from the Tribe Bocconieae (Papaveraceae): A Chemical and Biological Review
1
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
2
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
These authors contributed equally to the work.
*
Authors to whom correspondence should be addressed.
Received: 14 May 2014; in revised form: 12 August 2014 / Accepted: 20 August 2014 / Published: 25 August 2014

Abstract

:
The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the isolation and identification of a variety of molecules, has shed light on the tribe. Among those molecules, isoquinoline alkaloids, and their antimicrobial, antifungal, and anti-inflammatory activities are especially noteworthy. This paper presents a comprehensive compilation of current research progress, with emphasis on the alkaloids and their distribution, phytochemical and pharmacological investigation, toxicity and side effects, related chemotaxonomy and future use prospects, and hopefully provides a valuable reference as an effort to promote further exploration and application of this tribe.
Keywords:
Papaveraceae; Macleaya; Bocconia; alkaloids; bioactivity; review

1. Introduction

The Papaveraceous plants are very well-known for their extensive economic use as well as medicinal ones, which are directly associated with their rich production of alkaloids with novel structures and significant bioactivities. A variety of alkaloids, such as morphine, codeine, protopine, isocorydine, and tetrahydropalmatine, were discovered in this family, and they have irreplaceable therapeutic value in the treatment of many diseases.
The Bocconieae is a small tribe consisting of only two closely related genera, Macleaya and Bocconia, which share similarities in morphology and chemical components. The genus Macleaya contains two slightly toxic species, M. cordata (Willd.) R. Br. and M. microcarpa (Maxim.) Fedde, distributed in East Asia and widely found in South and Northwest China [1]. The genus Bocconia, on the other hand, includes ca. nine species, distributed mainly in tropical areas of Mexico, Central and Southern America [2].
The plants of the tribe Bocconieae play an important role as sources of traditional medicines for people in developing countries. For example, B. frutescens is used in Mexico to treat skin ulcers, dermatitis, and some respiratory tract infections, as well as tuberculosis [3]. B. arborea is employed for the treatment of diverse infectious diseases and is variously known in Mexico as llora sangre (weeping blood), cocoxíhuitl, ahuacachilli, mano de león (lion’s hand), palo del diablo (devil’s stick), palo amarillo (yellow stick). Native residents also use B. arborea as a purgative, vermifuge, antitumor, and anti-inflammatory agent to heal wounds and dissolve warts, or as a carminative agent to take advantage of its cathartic and analgesic activities [2,4]. M. cordata has been widely used as folk medicine in China, North America, and Europe, where it has been applied to cure cervical cancer and thyroid cancer, according to clinical records [5].
Modern chemistry and pharmacology research has revealed that alkaloids are the characteristic ingredients, overwhelming in quantity, and account for the major bioactivities of most Papaveraceous plants [6]. Therefore, this paper compiles complete data of alkaloids from the plants of the tribe Bocconieae, focusing on their distribution, isolation, structural features, and pharmacological activities, and hopefully may provide a useful reference for further studies on this tribe.

2. Chemical Constituents

A total of 75 alkaloids have been described from Bocconieae species so far, including the predominant benzophenanthridines (BPAs) 150, protoberberines 5164, protopines 6569 and other types 7075. Their structures are displayed in Figure 1 and Figure 2, and their names, corresponding source plants, parts, and references are listed in Table 1 and Table 2.
The BPA type of alkaloids, derived from protoberberines via N-C6 bond cleavage and the formation of C6-C13 bonds is one of the characteristic and chemotaxonomic components in the plants of the family Papaveraceae [7,8]. The BPAs in the plants of the tribe Bocconieae cover dihydrobenzophen-anthridines (120, 3236, 3942), quaternary BPAs (QBPAs, 2124, 2931), N-demethylated BPAs 2528, hexahydrobenzophenanthridines 3738, dimeric BPAs 4450, and the seco-BPA 43. Among them, some (compounds 4, 9, 10, 17, 18, 21, 29, 48, 49, 66, and 67) are widespread, especially 21, 29, and 6567, and some (compounds 4, 810, 16, and 30) are less abundant, while 51, 53 and 54 are scarce in this tribe. Dimers 4450 from B. arborea and M. microcarpa are considered artifacts probably derived from reactions occuring during the extraction and isolation, although the possibility their natural existence cannot be completely excluded, as similar dimers were also described in plants of the genus Dactylicapnos in the same family [9]. Compound 7 should not be a natural product, as it is obviously derived from the use of n-butanol during its extraction. Furthermore, compounds 56, 58, 59, and 7073 are obtained in cell cultures of M. cordata.
Figure 1. Structures of compounds 150 from the tribe Bocconieae.
Figure 1. Structures of compounds 150 from the tribe Bocconieae.
Molecules 19 13042 g001
Figure 2. Structures of compounds 5175 from Bocconieae.
Figure 2. Structures of compounds 5175 from Bocconieae.
Molecules 19 13042 g002
In addition to the major BPA alkaloids, other types of constituents, including phenolic acids, essential oil (2-methoxy-4-vinylphenol) [10,11], polysaccharides, flavonoids, steroids [12] from M. cordata, and a triterpene (3α-hydroxyolean-12-en-30-oic acid) from B. arborea [13] were also reported.
Besides distribution and structural features, determination of stereochemistry of the alkaloids is another important issue, not only for the structural elucidation, but also for the clarification of reaction mechanism(s), especially for those alkaloids with complex skeletons and more than one chiral center. The relative configurations of compounds 17 and 3234 were solved by X-ray single-crystal diffraction and analysis of circular dichroism data [14,15]. However, the absolute configurations of many of these alkaloids remaining unresolved, and in need of further research efforts.
Table 1. Alkaloids isolated from Bocconieae.
Table 1. Alkaloids isolated from Bocconieae.
NameTypePlantPartRef.
111-O-MethyldihydrochelerythrineIAB. arborea[16]
2Angoline ((±)-6-methoxydihydro-chelerythrine)IAM. cordataStems[17]
B. arboreaLeaves, stems[2]
M. microcarpaAerial parts, roots[14,18,19]
312-MethoxydihydrochelerythrineIAB. integrifoliaLeaves[20]
4DihydrochelerythrineIAB. integrifoliaLeaves[20]
B. arboreaAerial parts[4]
B. frutescensLeaves[3]
M. microcarpaRoots, leaves, whole plant[14,21,22]
M. cordata Fruits[23]
B. pearceiFruits[24]
56, 12-DimethoxydihydrocheleritrineIAB. arborea[25]
68-HydroxydihydrochelerythrineIAM. cordata.Seeds[26]
76-ButoxydihydrochelerythrineIAM. microcarpaRoots[14]
8OxychelerythrineIAB. pearceiFruits[24]
9OxysanguinarineIAB. latisepalaLeaves, roots, seeds[27]
B. arborea[16]
B. pearceiFruits[24]
M. cordata[10]
10DihydrosanguinarineIAM. cordataFruits[23]
B. integrifoliaLeaves[20]
B. arboreaAerial parts[4,16]
M. microcarpaRoots, leaves, whole plant[14,21,22]
B. PearceiFruits[24]
11DihydrochelirubineIAB. integrifoliaLeaves[20]
B. pearceiFruits[24]
126-MethoxydihydrosanguinarineIAM. cordataFruits[10]
M. microcarpaRoots[14]
138-MethoxydihydrosanguinarineIAM. cordataSeeds[26]
146-MethoxydihydrochelirubineIAB. arborea[25]
156-EthoxysanguinarineIAM. cordata[10]
M. microcarpaWhole plant[21]
16BocconolineIAB. cordata[28]
M. cordata[10]
17(±)-6-AcetonyldihydrochelerythrineIAB. arboreaBarks, aerial parts[2,15]
B. frutescensLeaves[3]
M. cordataFruits[10,23]
18(±)-6-AcetonyldihydrosanguinarineIAB. arboreaAerial parts[2]
B. frutescensLeaves[3]
M. cordataFruits[10,23]
M. microcarpaWhole plant[21]
19Spallidamine(6-Carboxymethyldihydrosanguinarie)IAM. microcarpaRoots[14]
M. cordataWhole plant[12]
206-CarboxymethyldihydrochelerythrineIAM. cordataWhole plant[12]
21ChelerythrineIBB. latisepalaBarks, stems, seeds[27]
M. cordata[29]
B. frutescensRoots, stalks and leaves[30]
M. microcarpa[31]
22ChelilutineIBM. cordataRoots[10]
M. microcarpa[31]
238-O-DemethylchelerythrineIBM. cordata[29]
246-EthoxychelerythrineIBM. cordata[10]
25NorsanguinarineICM. cordataFruits[10]
2612-MethoxynorchelerythrineICB. pearceiFruits[24]
27PancorineICM. microcarpaRoots[14]
28NorchelerythrineICM. cordataWhole plant[12]
29SanguinarineIBB. latisepalaBarks, stems[27]
B. cordataLeaves[32]
B. frutescensRoots, stalks and leaves[30]
M. cordata.Fruits[29,33]
M. microcarpaAerial parts[18,19,34]
30Bocconine (chelirubine)IBB. cordata[35]
M. microcarpa[31]
31MacarpineIBM. cordataCallus tissues[10,36]
M. microcarpa[31]
32Maclekarpine AIAM. microcarpaRoots[14]
33Maclekarpine BIAM. microcarpaRoots[14]
34Maclekarpine CIAM. microcarpaRoots[14]
356 α-IsobutanonyldihydrochelerythrineIAM. cordataFruits[23]
366 α-IsobutanonyldihydrosanguinarineIAM. cordataFruits[23]
37HomochelidonineIDM. cordata[10]
38ChelidonineIDB. frutescensRoots[37]
39Maclekarpine DIAM. microcarpaRoots[14]
40Maclekarpine EIAM. microcarpaRoots[14]
416-(1'-hydroxyethyl)-dihydrochelerythrineIAM. microcarpaRoots[14]
42R-6-((R)-1-Hydroxyethyl)-dihydrochelerythrieIAM. cordataWhole plant[12]
43ArnottianamideIFM. microcarpaRoots[14]
44ChelerythridimerineIEB. arboreaBarks[38]
45Bis[6-(5, 6-dihydrochelerythrinyl)]etherIEM. microcarpaRoots[14]
46(±)-SanguidimerineIEB. arborea Aerial parts[2]
M. cordataLeaves[10]
47ChelidimerineIEB. arborea Aerial parts[2]
M. cordataLeaves[10]
48(±)-Bocconarborine AIEB. arboreaAerial parts[2]
M. cordataLeaves[10]
M. microcarpaWhole plant[21]
49(±)-Bocconarborine BIEB. arboreaAerial parts[2]
M. cordataLeaves[10]
501, 3-Bis(1l-hydrochelerythriny1)acetoneIEB. arborea[16]
I: benzophenanthridine (BPA); IA: dihydrobenzophenanthridine; IB: QBPA; IC: N-demethylation BPA; ID: hexahydrobenzophenanthridine; IE: dimeric BPA; IF: seco-BPA.
Table 2. Alkaloids isolated from Bocconieae.
Table 2. Alkaloids isolated from Bocconieae.
NameTypePlantPartRef.
51BerberineIIB. frutescens
M. cordata
M. microcarpa
Roots, stalks, leaves

Roots
[30]
[10]
[31]
52BerberrabineIIM. microcarpaWhole plant[21]
53CoptisineIIB. frutescens
M. microcarpa
Roots, stalks and leaves
Roots
[30]
[31]
54CorysamineIIB. frutescens[37]
55ColumbamineIIB. frutescensRoots, stalks, leaves[30]
56DehydrocorytenchineIIM. cordataCultured cells[39]
57DehydrocheilanthifolineIIM. cordata[40]
58TetrahydropalmatrubineIIM. cordataCultured cells[39]
59CorytenchineIIM. cordataCultured cells[39]
60(–)-IsocorypalmineIIB. frutescensLeaves, roots[30,37,41]
61(–)-ScoulerineIIB. frutescensRoots, leaves[30,37]
62(–)-cis-N-MethylcanadiniumIIB. frutescensRoots[37]
63(–)-α-CanadineIIB. frutescensRoots, stalks, leaves[30]
64DehydrocicanthifolineIIM. cordata[40]
65β-AllocryptopineIIIM. microcarpaAerial parts, whole plant[18,19,21]
66α-AllocryptopineIIIB. cordata
M. cordata
B. latisepala
M. microcarpa
Leaves
Fruits
Roots
Whole plant
[32]
[10]
[27]
[21]
67ProtopineIIIB. latisepala
B.cordata
B. frutescens
M. cordata
M. microcarpa
Leaves, roots
Leaves
Roots, stalks, leaves
Cultured cells
Aerial parts, whole plant
[27]
[32]
[30,41]
[39]
[19,21]
68CryptopineIIIM. cordata
M. microcarpa
Fruits
Aerial parts
[10]
[18]
69Protopine N-oxideIIIB. cordataWhole plant[10,42]
70PapaverineIVM. cordataCultured cells[39]
71LaudanineIVM. cordataCultured cells[43]
72CodamineIVM. cordataCultured cells[43]
73PseudocodamineIVM. cordataCultured cells[43]
74RhoeadineIVB. frutescensLeaves, stalks[30,41]
75N-p-CoumaroyltyramineIVM. microcarpaRoots[14]
II: protoberberine; III: protopine; IV: other types.

3. Biological Activities

Crude extracts, essential oils and other individual compounds from the plants of the tribe Bocconieae display insecticidal, cough treatment, antitumor and antifungal activities. Among all investigations, M. cordata is the most addressed species.

3.1. Cytotoxicity against Tumor Cells

The in vitro anticancer properties of crude extract of M. cordata were assessed against MRC5 fetal lung fibroblasts and A549 adenocarcinomic epithelial cells. Viability of the treated MRC5 cells was reduced in a concentration-dependent manner, demonstrating that the normal lung cells are sensitive to the extract. Surprisingly, the A549 viability was slightly increased in response to extract exposure at a low concentration, whereas the viability was reduced accordingly at higher concentrations [44]. Fractions from the ethanol extract of the roots of M. microcarpa exhibited cytotoxicity against the Bel-7402, BGC-823, HCT-8, A2780 and A549 cell-lines, with IC50 values in the 1.1–23.8 μg/mL range [14].
The total alkaloids of M. cordata showed in vivo inhibitory activity against transplanted tumors in mice in a dose-dependent manner [45], and further in vitro assessment of total alkaloids of M. cordata showed significantly inhibitory activity against the proliferation of human Hep3B cells and murine H22 cells, with IC50 values of 2.0–3.0 μg/mL. The total alkaloids of M. cordata also inhibited the development of tumors and prolonged the survival of S180 tumor-bearing mice [46].
It was reported that chelerythrine (CHE, 21) inhibited the proliferation of BGC-823 human gastric cancer cells in a time- and dose-dependent manner, accompanied with S phase arrest. It also induced apoptosis by a mechanism involving a reduction in the mitochondrial membrane potential, the release of cytochrome c, activation of caspase 3 and cleavage of poly-ADP-ribose polymerase (PARP). In addition, CHE-induced apoptosis was accompanied by down-regulation of Bcl-xl and Bcl-2 proteins without change in the levels of Bax proteins [47]. Compounds 7, 12 and 34 displayed marked cytotoxicities against the Bel-7402, BGC-823, HCT-8, A2780 and A549 cell-lines, with IC50 values of 0.5–3.4 μM, equal to the positive control camptothecin (0.28 to 3.15 μM) [14]. Adhami et al demonstrated that sanguinarine (SAN, 29) caused cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery [48]. Furthermore, SAN induced apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3 cells via modulations in Bcl-2 family proteins [49], and induced apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion [50].
Besides, protopine (PRO, 67), cryptopine (CRY, 68) and allocryptopine (ALL, 65/66) potently inhibited human cytochrome P450 (CYP) 2D6, with IC50 values lower than 1 μM. PRO and CRY moderately inhibited CYP2C19 with IC50 values of 1–10 μM [51].

3.2. Insecticidal Activities

Ethanolic extract of the seeds of M. cordata showed a significant insecticidal effect against the growth of the cotton aphid Aphis gossypii Glover [26]. Crude extracts and fractions from the leaves of M. cordata were investigated in vitro against the fish parasite Ichthyophthirius multifiliis by a bioactivity-guided isolation method, and caresults showed that chloroform extract exhibited promising activity with 100% antiparasitic efficacy at the concentration of 70.0 mg/L after 4 h of exposure [52]. The chloroform extract of the leaves of M. microcarpa also showed a promising antiparasitic activity against I. multifiliis [22].
Compounds 4 and 10 showed potent activity against I. multifiliis with EC50 values of 9.43 mg/L and 5.18 mg/L, respectively, after 48 h of exposure [22]. SAN (29) exhibited a remarkable inhibitory effect against I. multifiliis at a concentration of 0.7 mg/L, with an LC50 value of 0.437 mg/L after 4 h of exposure. In vivo antiparasitic efficacy tests showed that the number of I. multifiliis on the gills in the treatment group (in 0.9 mg/L SAN) was reduced by 96.8% in comparison to the untreated at 25 °C for 48 h. There were no deaths in the treatment group during the trial compared with a 40% death rate of the untreated fish [52]. Compound 10 showed significant inhibitory activity against Leishmania with an IC50 value of 0.014 μg/mL, followed by compounds 4 and 11 with the same IC50 value of 0.166 μg/mL [24]. Compounds 6 and 13 demonstrated an effect in decreasing the survival rate of the cotton aphid by 76.1% ± 7.9% and 73.6% ± 14.6% at 100 ppm, respectively [26]. The bisulfates of CHE, SAN and total alkaloids from the fruits of M. cordata have molluscicidal activities against the snail Oncomlania hupensis, the intermediate host of schistosomiasis, in both time-and concentration-dependent manners, with LC50 values at 72 h of 2.05, 0.19, and 0.40 mg/L, respectively [53].
Wang et al. reported that the extract of aerial parts of M. microcarpa and isolates (2, 29, 65, 67, and 68), especially SAN (29), might be useful for the treatment of Dactylogyrus intermedius infections. Another in vivo anthelmintic assay backed the theory by reporting evident inhibitory effects with EC50 values of 0.37–8.13 mg/L [19].

3.3. Antimicrobial Activity

The plants of Bocconieae species, such as B. arborea [54] and B. frutescens [3], exhibited strong antimicrobial activity, therefore they have been applied extensively as traditional medicines for the treatment of diverse infectious diseases.
Methanolic extract of the leaves of B. arborea showed a general antimicrobial effect against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa at 10 mg/mL and below [55]. Both ethanolic extract of leaves and hexane extract of stems of B. frutescens showed strong activities against E. coli and S. aureus [3]. Moreover, methanol and hexane extracts of B. frutescens leaves displayed in vitro antimycobacterial activity against Mycobacterium tuberculosis with the same MIC value of 125 μg/mL [56].
The bisulfates of quaternary benzophenanthridines from M. cordata showed strong inhibitory effects against Elsinoe ampelina, Colletotrichum gloeosporioides, Cercospora viticola, Pyricularia oryzae, Gibberella zeae, and Phytophythora capsici, with EC50 values of 3.35–10.08 μg/mL [57]. Also, extracts from M. cordata formulated at 150 mg/L QBPA are used to spray greenhouse roses (Rosa sp.) infected by Sphaerotheca pannosa var. rosae (powdery mildew) at 10-day intervals. One day after application, symptoms of mildew infection show visible reduction by 60%. Subsequent studies demonstrated that a tank of QBPAs provided enhanced control of powdery mildew on roses [58].
Methanolic extract of B. frutescens showed moderate inhibitory activity against Trichomonas vaginalis with annn IC50 value of 30.9 μg/mL [59]. Crude alcoholic extracts of different parts of fresh or dried B. frutescens possessed antimalarial activity. Compared to dried raw materials, extract of the fresh plant exhibited a higher inhibitory effect against Plasmodium berghei, especially of fresh green fruits (IC50 2.4 μg/mL) [60]. QBPAs from the plants of the genus Macleaya are effective in the control of many fungal diseases. Methanolic extract of the leaves of B. arborea exhibited anti-yeast activity against Candida albicans with MIC value of 2.5 mg/mL [55].
Compounds 4 and 10 displayed significant antimicrobial activities against S. aureus, Streptococcus faecalis, Proteus mirabilis, and E. coli with MIC values of 9.3–300 μg/mL [4]. Besides, they also exhibited the highest in vitro antifungal activity against Botrytis cinerea Pers with inhibitory rates of 98.32% and 95.16% at 50 μg/mL, respectively, for they inhibit spore germination in a concentration-dependent manner. Moreover, they showed potent in vivo protective and curative effects on Erysiphe graminis and B. cinerea [61]. Compounds 2 and 14 both had the same MIC value of 12.5 μg/mL against a sensitive strain of M. tuberculosis H37Rv [25]. Compound 2 also exhibited activity against S. aureus and S. faecalis, with a MIC value around 25 μg/mL [2]. Further, 2, 4 and 10 exhibited anti-yeast activity against Candida albicans with MIC values of 12.0, 18.7 and 18.7 μg/mL, respectively, while nystatin was 5.0 μg/mL [2,4].
CHE (21) and SAN (29) demonstrated a significant antifungal activity against Rhizoctonia solani with IC50 values of 0.55 and 0.47 μg/mL, respectively. They are also effective against Botryosphaeria bernegeriana, Botrytis cinerea, Fusarium graminearum, F. oxysporum f.sp. lycopersici, F. oxysporum f.sp. vasinfectum, Magnaportheoryzae, and R. solani [62]. In most of the bacterial strains used, such as S. aureus CCM 3953, S. aureus CCM 4223, P. aeruginosa CCM 3955, two strains of E. coli (CCM 4225 and CCM 3954), and Streptococcus agalactiae, the antimicrobial activity increased as the concentration increased, which means the pure CHE and SAN exhibited the most potent effect. PRO (67) and ALL (65/66) showed weaker antimicrobial activity than CHE and SAN, and dihydrosanguinarine (10) had a mild inhibitory effect with MIC value around 500 μg/mL, whereas 4 was inactive [10].
Besides, angoline (2), SAN, ALL, and CRY (68) also showed in vitro activities against fish pathogenic bacteria Aeromonas hydrophila, A. salmonicida, Vibrio anguillarum and V. harveyi with MIC values of 12.5–200 mg/L compared with florfenicol 0.5–2.0 mg/L [18].

3.4. Anti-Inflammatory Property

Some of the plants of this tribe have been shown to possess anti-inflammatory properties. The aqueous plant extract of B. arborea showed anti-inflammatory activity and is recommended for medical use in the treatment of oral inflammatory processes [38]. Extracts from M. cordata are also used in traditional medicine for their anti-inflammatory activity [62,63].
Research on anti-inflammatory activity has been primarily focused on possible interactions with the nuclear factor-κB (NF-κB) pathway which plays an important role in regulating the expression of cyclooxygenase-2 and pro-inflammatory cytokines. In cell models, SAN was found to inhibit NF-κB activation and CHE suppressed inducible expression of cyclooxygenase-2. The anti-inflammatory action of CHE and SAN could also be associated with their ability to inhibit formation of superoxide radical by phagocyte NADPH oxidase. In contrast, the relevant molecular targets of PRO and ALL (65/66) have not been identified to date [64]. CHE and SAN exhibited local anti-inflammatory effects in the carrageenan-induced pawedema test in rats. SAN but not CHE inhibited the signal transduction pathways critical to the inflammatory response leading to NF-κB activation [63].

3.5. Effect on Cardiovascular System

The aqueous extract of B. frutescens possessed potent stimulatory effects with an EC50 of 18 ± 2.4 μg/mL, which presented maximum contractile response (Emax = 80.6 ± 5.6%) when the vascular tone changed [65]. The methanolic and dichloromethane extracts of the roots of B. frutescens inhibited [3H]-angiotensin II binding (AT II, AT1 receptor) by more than 50% [66].
CHE and SAN were significant inhibitors of [3H]-AT II binding (hAT1 receptor) with IC50 values 9.93 and 1.90 μM, respectively. On the other side, the cyclo(-d-Trp-d-Asp-[prolyl-3, 4(n)-[3H]]Pro-d-Val-Leu) binding ([3H]-BQ-123, ETA receptor) was mildly inhibited [37].
SAN interacted with the human AT1 receptor in a slow, nearly irreversible and non-competitive manner. The inhibition of [3H] (2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimid-azoline-7-carboxylic acid) ([3H]candesartan) binding by SAN was independent of cell viability, since the alkaloid inhibited both intact Chinese hamster ovary (CHO) cells transfected with human AT1 receptor and with their cell membranes (Ki = 0.14 and 1.10 μM, respectively) at a similar extent radioligand binding [67].

3.6. Other Activities

The aqueous extract of B. frutescens showed significant antisecretory activity with inhibitory rates of 86.0% at 300 mg/kg on cholera toxin-induced intestinal secretion in rat jejunal loops model [68]. M. cordata root powder could improve liver function in acute hepatic injuries. M. cordata could lessen the level of serum lactate dehydrogenase (LDH) and mortality rate of rats, while increasing the ratio of serum albumin/globulin (A/G), protecting cellular membrane effectively and inhibiting fibrosis in rats with chromic hepatic injury caused by tetrachloromethane. Furthermore, it enhanced the function of T and B lymphocytes [69]. The methanol extract of aerial parts of M. cordata exhibited strong antioxidative activity against total reactive oxygen species (ROS), with an IC50 value of 1.7 μg/mL, compared to the positive control Trolox (7.61 ± 0.12 μg/mL) [70]. The alkaloids from fruits of M. cordata collected in different regions possessed different antioxidant activities, with IC50 values ranging from 578 to 1,192 mg/L [71].
CHE and SAN, and their mixture (sanguiritrin) from M. cordata were inhibitors of aminopeptidase A and dipeptidyl peptidase IV. They inhibited amino peptidase N by 82%, 82%, and 88%, DPP IV by 38%, 62%, and 57%, respectively, at 50 mM. When bovine serum albumin (500 μg/mL) was added, the inhibition of both proteases by QBPA at 50 μM was significantly diminished, which suggested that strong interaction of CHE and SAN with bovine and human serum albumin was proved by electrophoretic determination of their respective conditional binding constants [72]. CHE, SAN and QBPA extract from M. cordata exerted differential inhibitory effects against hydrolytic activity of particular dipeptidyl peptidase (DPP)-like enzyme isolated from human blood plasma and from human and rat glioma cell lines. The low-MW form of DPP-IV-like enzyme activity, corresponding most probably with DPP-8, observed only in glioma cells but not in human plasma, was inhibited preferentially by CHE, SAN and the QBPA extract, indicating that some QBPA’s biological effects could be determined by tissue and cell type specific dipeptidyl peptidase IV-like molecules expression pattern [73]. SAN may, under appropriate conditions, increase the capacity of the enzymatic antioxidant defense system via activation of the p38 MAPK/Nrf2 pathway [64].
The alkaloids of M. cordata are the major active ingredients in Sangrovit, a phytogenic feed additive composed mainly of CHE and SAN. Jankowski et al. found that feeding broilers with 20 mg/kg of Sangrovit led to a significant increase of mucosal maltase, reduced duodenal villus height yet no change in pH in the small and lower intestine [74]. Despite lacking of improvement in final body weight, a low dose of dietary Sangrovit was found to exert positive effects on caecal metabolism of broilers [75]. In addition, macarpine (31), a QBPA described only in two species, was recently reported as promising fluorescent probe for labeling of cell nuclei at fluorescence microscopy and flow cytometry [31].

4. Toxicity and Side Effects

Modern pharmacological studies show that the QBPA bisulfates from M. cordata exhibited low toxicity in acute oral, acute inhalation and acute dermal toxicity tests, and no stimulating effect on the skin, but weak sensitization and severe irritation to the eyes [57]. It was reported in China that one person who ate bee slag containing M. cordata appeared to show symptoms like dizziness, tinnitus, numbness, and nausea [76]. There was another report that one female died after taking about 250 mL of fresh root decoction (125 g/250 mL) of M. cordata, supposedly used for curing joint pain [77].
The subchronic safety of sanguiritrin was assessed by feeding rats a diet containing 120 ppm (100 ppm QBPA) for 109 days, but no adverse effects were observed on rat organism, including no influence on the gut mucosal epithelium, liver tissue and any biochemical parameters. Oxidative stress did not manifest during the experiment [78]. The sensory evaluation of broiler breast and thigh meat did not reveal any negative influence of dietary supplementation with a 30 mg/kg dose of the alkaloid-containing preparation Sangrovitin for 5 week [79]. Rawling, et al. reported that low levels of Sangrovit (25–100 mg/kg) had a positive effect on tilapia growth performance with no apparent effects on carcass composition, hepatic function or health status [80]. Besides, the effects of daily administration of the extract from M. cordata (2 and 100 mg/kg feed, SAN:CHE = 3:1) in the diet on the health status of swine were evaluated, and the results showed that an average daily oral dose of alkaloids up to 5 mg/kg animal body weight proved to be safe [81]. The cytotoxicity analysis on primary cultures of human hepatocytes suggested that CHE and dihydrochelerythrine (4) were nontoxic up to 50 μM concentration [82]. However, the aqueous extracts of the dry roots of M. microcarpa showed toxic effect against growth of cultured algae (P. subcapitata and S. quadricauda) and cyanobacteria (M. aeruginosa and S. leopoliensis), with EC50 values of 626.90–984.81 mg/L [83].
SAN had been reported to form DNA adducts in vitro and to increase the levels of DNA single strand cleavage in the blood and bone marrow of mice injected intraperitoneally. There was no genotoxic effects of orally administrated 120 mg/kg feed Sangrovit in pigs or rats in a 90-day observation. M. cordata extract and/or Sangrovit induced no DNA damage to rat lymphocytes or hepatocytes after 90-days oral administration [84]. Some parameters of dextran sulfate sodium (DSS)-induced colitis were improved by adding 500 ppm Sangrovit to feed the rats. For example, it showed less severe damage to the colon mucosa and decreased histological colitis scores. What’s more, it showed a diminished expression of DSS-induced COX-2, significantly mitigating myeloperoxidase activity in colon tissue and reducing level of glutathione in erythrocytes [63]. Broadly, the Bocconieae alkaloids are considerable toxic to some extent, and for application of the extracts and pure alkaloids from the tribe attention must be paid to their side effects.

5. Discussion and Conclusions

A total of 75 alkaloids were described from the plants of the tribe Bocconieae so far, including benzophenanthridines, protoberberines, protopines, and others. Some exhibited such a variety of biological effects such as antitumor, insecticidal, and antimicrobial activities. SAN (29) has shown a promising future as a lead compound for the development of biological pesticides. Meanwhile, the side effects of the plants of this tribe should also be given adequate attention.
Currently, there are two opposing opinions when it comes to the classification system: one suggests that Macleaya and Bocconia should be classified as the tribe Bocconieae, which is documented in the Hutchinson System, while the other insists that Macleaya and Bocconia should be placed in Chelidonieae, because of the characteristic alkaloids, especially CHE and SAN, generally occurred in the Chelidonieae. Our present review reveals that there is no obvious difference in alkaloids observed in these two genera compared with those from Chelidonieae, and therefore provides chemotaxonomic evidence supporting the latter classification, although more substantial evidence is needed to determine the final taxonomy of these genera.
Since the plants of the tribe Bocconieae have ecological adaptability advantages, and are easy to cultivate and manage, their exploitation and utilization as natural antimicrobials have attracted much attention around the world. For instance, the alkaloids from M. cordata were used by United States as breath freshener and air freshener [85].
Overall, as an alkaloid-rich source, further in-depth research on the plants of the tribe Bocconieae, regarding their phytochemical investigation, determination of stereochemistry, in vivo and in vitro biological evaluation, and economic exploration, are of great significance and positively called for.

Acknowledgments

The authors would like to thank Miss Ding W.J. (Beijing University of Chinese Medicine) who thoroughly polished the English in the article for us.

Author Contributions

Xuelong Yu and Xiaoli Gao drafted and revised the manuscript, Zhixiang Zhu, Yuan Cao and Qian Zhang made suggestions and played an important role in preparing this paper, and Xingyun Chai and Pengfei Tu approved the final version.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Institute of Botany, the Chinese Academy of Sciences. Iconographia Cormophytorum Sinicorum; Science Press: Beijing, China, 1994; Volume 2, p. 4. [Google Scholar]
  2. Julian, A.; Delgado, G. (±)-Bocconarborines A and B, novel 1, 3-bis-benzo[c]phenanthridinyl acetone alkaloids from Bocconia arborea. Rev. Soc. Quim. Mex. 2001, 45, 189–194. [Google Scholar]
  3. Sanchez-Arreola, E.; Hernandez-Molina, L.R.; Sanchez-Salas, J.L.; Martinez-Espino, G. Alkaloids from Bocconia frutescens and biological activity of their extracts. Pharm. Biol. 2006, 44, 540–543. [Google Scholar] [CrossRef]
  4. Navarro, V.; Delgado, G. Two antimicrobial alkaloids from Bocconia arborea. J. Ethnopharmacol. 1999, 66, 223–226. [Google Scholar] [CrossRef]
  5. Pi, G.P.; Ren, P.; Yu, J.M.; Shi, R.F.; Yuan, Z.; Wang, C.H. Separation of sanguinarine and chelerythrine in Macleaya cordata (Willd) R. Br. based on methyl acrylate-co-divinylbenzene macroporous adsorbents. J. Chromatogr. A 2008, 1192, 17–24. [Google Scholar] [CrossRef]
  6. Guo, Z.Q.; Guo, Q.; Zhang, S.Y.; Li, C.; Chai, X.Y.; Tu, P.F. Chemical constituents from the aerial parts of Meconopsis horridula (Papaveraceae). Biochem. Syst. Ecol. 2014, 55, 329–332. [Google Scholar] [CrossRef]
  7. Slaninova, I.; Pencikova, K.; Urbanova, J.; Slanina, J.; Taborska, E. Antitumour activities of sanguinarine and related alkaloids. Phytochem. Rev. 2014, 13, 51–68. [Google Scholar] [CrossRef]
  8. Su, Z.W. The chemotaxonomy of angiosperms families (V): Papaveraceae. J. Int. Pharm. Res. 1981, 2, 65–70. [Google Scholar]
  9. Zhang, G.L.; Ruecker, G.; Breitmaier, E.; Nieger, M.; Mayer, R.; Steinbeck, C. Alkaloids from Dactylicapnos torulosa. Phytochemistry 1995, 40, 299–305. [Google Scholar] [CrossRef]
  10. Kosina, P.; Gregorova, J.; Gruz, J.; Vacek, J.; Kolar, M.; Vogel, M.; Roos, W.; Naumann, K.; Simanek, V.; Ulrichova, J. Phytochemical and antimicrobial characterization of Macleaya cordata herb. Fitoterapia 2010, 81, 1006–1012. [Google Scholar] [CrossRef]
  11. Chen, L.J.; Zhou, S.Y.; Shi, H.Z.; Yin, J. Determination of Chemical Composition of the Essential Oil from Macleaya cordata by GC-MS. Chin. Agric. Sci. Bull. 2009, 25, 94–96. [Google Scholar]
  12. Xiao, H.J. Study on the Chemical Constituents and their Bioactivities from Macleaya cordata. Master Thesis, Tianjin Medical University, Tianjin, China, 2013. [Google Scholar]
  13. Chavez, M.I.; Julian, A.; Delgado, G. Structure elucidation and 13C-NMR spectral assignments of 3α-hydroxyolean-12-en-30-oic acid, a new triterpene from Bocconia arborea. Magn. Reson. Chem. 2003, 41, 143–144. [Google Scholar] [CrossRef]
  14. Deng, A.J.; Qin, H.L. Cytotoxic dihydrobenzophenanthridine alkaloids from the roots of Macleaya microcarpa. Phytochemistry 2010, 71, 816–822. [Google Scholar] [CrossRef]
  15. Martinez-Martinez, F.J.; Padilla-Martinez, I.I.; Hernandez-Carlos, B.; Perez-Gutierrez, R.M.; Garcia-Baez, E.V. X-ray diffraction and total 1H and 13C NMR assignment of (RS)-5,6-dihydro-7, 8-dimethoxy-5-methyl-6-(2-oxopropyl)-(2,3-methylenedioxyphenyl)-[c]-phenanthridine ((RS)-6-acetonyldihydrochelerythrine). J. Chem. Crystallogr. 2002, 32, 63–68. [Google Scholar] [CrossRef]
  16. MacLean, D.B.; Gracey, D.E.F.; Saunders, J.K.; Rodrigo, R.; Manske, R.H.F. Benzophenanthridine alkaloids from Bocconia arborea. Can. J. Chem. 1969, 47, 1951–1956. [Google Scholar] [CrossRef]
  17. Lee, S.K.; Qing, W.G.; Mar, W.; Luyengi, L.; Mehta, R.G.; Kawanishi, K.; Fong, H.H.S.; Beecher, C.W.W.; Kinghorn, A.D.; Pezzuto, J.M. Angoline and chelerythrine, benzophenanthridine alkaloids that do not inhibit protein kinase C. J. Biol. Chem. 1998, 273, 19829–19833. [Google Scholar] [CrossRef]
  18. Kang, Y.J.; Yi, Y.L.; Zhang, C.; Wu, S.Q.; Shi, C.B.; Wang, G.X. Bioassay-guided isolation and identification of active compounds from Macleaya microcarpa (Maxim) Fedde against fish pathogenics bacteria. Aquac. Res. 2013, 44, 1221–1228. [Google Scholar]
  19. Wang, G.X.; Zhou, Z.; Jiang, D.X.; Han, J.; Wang, J.F.; Zhao, L.W.; Li, J. In vivo anthelmintic activity of five alkaloids from Macleaya microcarpa (Maxim) Fedde against Dactylogyrus intermedius in Carassius auratus. Vet. Parasitol. 2010, 171, 305–313. [Google Scholar] [CrossRef]
  20. Oechslin, S.M.; Koenig, G.M.; Oechslin-Merkel, K.; Wright, A.D.; Kinghorn, A.D.; Sticher, O.; Miyagawa, M. An NMR study of four benzophenanthridine alkaloids. J. Nat. Prod. 1991, 54, 519–524. [Google Scholar] [CrossRef]
  21. Yang, X.J.; Miao, F.; Zheng, F.; Zhou, L.; Wang, X.; Geng, H.L.; Sun, W. Isolation and identification of alkaloids from Macleaya microcarpa (Maxim.) Fedde. Acta Bot. Boreal-Occident. Sin. 2010, 30, 405–411. [Google Scholar]
  22. Yao, J.Y.; Zhou, Z.M.; Li, X.L.; Yin, W.L.; Ru, H.S.; Pan, X.Y.; Hao, G.J.; Xu, Y.; Shen, J.Y. Antiparasitic efficacy of dihydrosanguinarine and dihydrochelerythrine from Macleaya microcarpa against Ichthyophthirius multifiliis in richadsin (Squaliobarbus. curriculus). Vet. Parasitol. 2011, 183, 8–13. [Google Scholar] [CrossRef]
  23. Feng, F.; Ye, F.Z.; Li, C.L.; Liu, W.Y.; Xie, N. New benzophenanthridine isoquinoline alkaloids from Macleaya cordata. Chin. J. Nat. Med. 2012, 10, 378–382. [Google Scholar]
  24. Fuchino, H.; Kawano, M.; Mori-Yasumoto, K.; Sekita, S.; Satake, M.; Ishikawa, T.; Kiuchi, F.; Kawahara, N. In vitro leishmanicidal activity of benzophenanthridine alkaloids from Bocconia pearcei and related compounds. Chem. Pharm. Bull. 2010, 58, 1047–1050. [Google Scholar] [CrossRef]
  25. Rayo Camacho-Corona, M.; Jesus Favela-Hernandez, J.M.; Gonzalez-Santiago, O.; GarzaGonzalez, E.; Molina-Salinas, G.M.; Said-Fernandez, S.; Delgado, G.; Luna-Herrera, J. Evaluation of some plant-derived secondary metabolites against sensitive and multidrug-resistant Mycobacterium tuberculosis. J. Mex. Chem. Soc. 2009, 53, 71–75. [Google Scholar]
  26. Baek, M.Y.; Park, H.J.; Kim, G.M.; Lee, D.Y.; Lee, G.Y.; Moon, S.J.; Ahn, E.M.; Kim, G.S.; Bang, M.H.; Baek, N.I. Insecticidal alkaloids from the seeds of Macleaya cordata on cotton aphid (Aphis gossypii). J. Korean Soc. Appl. Biol. Chem. 2013, 56, 135–140. [Google Scholar] [CrossRef]
  27. Dominguez, X.A.; Delgado, J.G.; Monroy C., A.; Armendariz, L.G.; Alcala, A.; Quevedo, J.; Rojas, P. A chemical study of Bocconia latisepala Wat. Can. J. Chem. 1965, 43, 679–682. [Google Scholar] [CrossRef]
  28. Ishii, H.; Hosoya, K.; Takao, N. Bocconoline: A new type dihydrobenzo[c]phenanthridine alkaloid possessing a unique substituent at C6 position. Tetrahedron Lett. 1971, 12, 2429–2432. [Google Scholar] [CrossRef]
  29. Tolkachev, O.N.; Savina, A.A.; Sheichenko, V.I.; Proskudina, V.V. 8-O-demethylchelerythrine from Macleaya cordata. Pharm. Chem. J. 1999, 33, 86–87. [Google Scholar] [CrossRef]
  30. Taborska, E.; Veznik, F.; Slavik, J. Alkaloids of the Papaveraceae. LXXI. Alkaloids from Bocconia frutescens L. Collect. Czech. Chem. Commun. 1980, 45, 1301–1304. [Google Scholar] [CrossRef]
  31. Pěnčíková, K.; Urbanová, J.; Musil, P.; Táborská, E.; Gregorová, J. Seasonal variation of bioactive alkaloid contents in Macleaya microcarpa (Maxim.) Fedde. Molecules 2011, 16, 3391–3401. [Google Scholar] [CrossRef]
  32. Kiryakov, N.G.; Kitova, M.S.; Georgieva, A.V. Alkaloids of Bocconi acordata. Cr. Acad. Bulg. Sci. 1967, 20, 189–192. [Google Scholar]
  33. Luo, X.B.; Chen, B.; Yao, S.Z. Rapid determination of protopine, allocryptopine, sanguinarine and chelerythrine in fruits of Macleaya cordata by microwave-assisted solvent extraction and HPLC-ESI/MS. Phytochem. Anal. 2006, 17, 431–438. [Google Scholar] [CrossRef]
  34. Onda, M.; Abe, K.; Yonezawa, K.; Esumi, N.; Suzuki, T. Constituents of Bocconia cordata. II. Bocconine. Chem. Pharm. Bull. 1970, 18, 1435–1439. [Google Scholar] [CrossRef]
  35. Konda, Y.; Harigaya, Y.; Onda, M. Studies on the constituents of Bocconia cordata. III. Structure elucidation of bocconine by means of nuclear magnetic resonance spectroscopic studies. J. Heterocycl. Chem. 1986, 23, 877–879. [Google Scholar] [CrossRef]
  36. Takao, N.; Kamigauchi, M.; Okada, M. Biosynthesis of benzo[c]phenanthridine alkaloids sanguinarine, chelirubine and macarpine. Helv. Chim. Acta 1983, 66, 473–484. [Google Scholar] [CrossRef]
  37. Caballero-George, C.; Vanderheyden, P.M.L.; Apers, S.; van den Heuvel, H.; Solis, P.N.; Gupta, M.P.; Claeys, M.; Pieters, L.; Vauquelin, G.; Vlietinck, A.J. Inhibitory activity on binding of specific ligands to the human angiotensin II AT1 and endothelin 1 ETA receptors: Bioactive benzo[c]phenanthridine alkaloids from the root of Bocconia frutescents. Planta Med. 2002, 68, 770–775. [Google Scholar] [CrossRef]
  38. Gutierrez, R.M.; Vargas Solis, R.; Diaz Gutierrez, G.; Martinez-Martinez, F.J. Identification of benzophenanthridine alkaloids from Bocconia arborea by gas chromatography-mass spectrometry. Phytochem. Anal. 2002, 13, 177–180. [Google Scholar] [CrossRef]
  39. Iwasa, K.; Cui, W.; Sugiura, M.; Takeuchi, A.; Moriyasu, M.; Takeda, K. Structural analyses of metabolites of phenolic 1-benzyltetrahydroisoquinolines in plant cell cultures by LC/NMR, LC/MS, and LC/CD. J. Nat. Prod. 2005, 68, 992–1000. [Google Scholar] [CrossRef]
  40. Wu, M.L.; Zhang, D.Z.; Xu, Q.J.; Xie, R.R.; Li, Q.Q. Advance in studies on Macleaya cordata. Asia-Pac. Tradit. Med. 2009, 5, 144–145. [Google Scholar]
  41. Slavik, J.; Slavikova, L. Alkaloids of Papaveraceae. LIX. Alkaloids from the leaves of Bocconia frutescens L. Collect. Czech. Chem. Commun. 1975, 40, 3206–3210. [Google Scholar] [CrossRef]
  42. Iwasa, K.; Okada, M.; Takao, N. Protopine-N.-oxide, an alkaloid from Bocconia cordata. Phytochemistry 1983, 22, 627–628. [Google Scholar] [CrossRef]
  43. Iwasa, K.; Doi, Y.; Takahashi, T.; Cui, W.; Nishiyama, Y.; Tode, C.; Moriyasu, M.; Takeda, K.; Minami, H.; Ikezawa, N.; et al. Enantiomeric separation of racemic 1-benzyl-N-methyltetrahydroisoquinolines on chiral columns and chiral purity determinations of the O-methylated metabolites in plant cell cultures by HPLC-CD on-line coupling in combination with HPLC-MS. Phytochemistry 2009, 70, 198–206. [Google Scholar] [CrossRef]
  44. Liu, M.; Lin, Y.L.; Chen, X.R.; Liao, C.C.; Poo, W.K. In vitro assessment of Macleaya cordata crude extract bioactivity and anticancer properties in normal and cancerous human lung cells. Exp. Toxicol. Pathol. 2013, 65, 775–787. [Google Scholar] [CrossRef]
  45. Fan, S.L.; Jiao, F.; Zhang, Y.; An, C.X.; Fu, J.M. Study on the effects of total alkaloids from Macleaya cordata on transplantable animal tumors. Shanxi Oncol. Med. 2000, 8, 174–149. [Google Scholar]
  46. Pang, J.X.; Ma, R.Q.; Liu, L.M.; Jiang, Y.P.; Sun, L.S. Total alkaloid of Macleaya cordata: In vitro cytotoxic effect on Hep3B cells and in vivo antitumor effect in mice. J. First Mil. Med. Univ. 2005, 25, 325–328. [Google Scholar]
  47. Zhang, Z.F.; Guo, Y.; Zhang, L.W.; Zhang, J.B.; Wei, X.H. Chelerythrine chloride from Macleaya cordata induces growth inhibition and apoptosis in human gastric cancer BGC-823 cells. Acta Pharm. Sin. B 2012, 2, 464–471. [Google Scholar] [CrossRef]
  48. Adhami, V.M.; Aziz, M.H.; Reagan-Shaw, S.R.; Nihal, M.; Mukhtar, H.; Ahmad, N. Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery. Mol. Cancer Ther. 2004, 3, 933–940. [Google Scholar]
  49. Ahsan, H.; Reagan-Shaw, S.; Breur, J.; Ahmad, N. Sanguinarine induces apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3 cells via modulations in Bcl-2 family proteins. Cancer Lett. 2007, 249, 198–208. [Google Scholar] [CrossRef]
  50. Jang, B.C.; Park, J.G.; Song, D.K.; Baek, W.K.; Yoo, S.K.; Jung, K.H.; Park, G.Y.; Lee, T.Y.; Suh, S.L. Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion. Toxicol. In Vitro 2009, 23, 281–287. [Google Scholar] [CrossRef]
  51. Salminen, K.A.; Meyer, A.; Jerabkova, L.; Korhonen, L.E.; Rahnasto, M.; Juvonen, R.O.; Imming, P.; Raunio, H. Inhibition of human drug metabolizing cytochrome P450 enzymes by plant isoquinoline alkaloids. Phytomedicine 2011, 18, 533–538. [Google Scholar]
  52. Yao, J.Y.; Shen, J.Y.; Li, X.L.; Xu, Y.; Hao, G.J.; Pan, X.Y.; Wang, G.X.; Yin, W.L. Effect of sanguinarine from the leaves of Macleaya cordata against Ichthyophthirius multifiliis in grass carp (Ctenopharyngodon idella). Parasitol. Res. 2010, 107, 1035–1042. [Google Scholar] [CrossRef]
  53. Zhong, M.; Li, G.Y.; Zeng, J.G.; Zhang, L.; Huang, K.L.; She, J.M.; Li, X.; Wei, W.Y. Evaluation of molluscicidal activities of benzo[c]phenanthridine alkaloids from Macleaya cordata (Wild) R. Br. on snail hosts of Schistosoma japonicum. J. Med. Plant. Res. 2011, 5, 521–526. [Google Scholar]
  54. Navarro, V.; Rojas, G.; Delgado, G.; Lozoya, X. Antimicrobial compounds detected in Bocconia arborea extracts by a direct bioautographic method. Arch. Med. Res. 1998, 29, 191–194. [Google Scholar]
  55. Navarro, V.; Villarreal, M.L.; Rojas, G.; Lozoya, X. Antimicrobial evaluation of some plants used in Mexican traditional medicine for the treatment of infectious diseases. J. Ethnopharmacol. 1996, 53, 143–147. [Google Scholar] [CrossRef]
  56. Cruz-Vega, D.E.; Verde-Star, M.J.; Salinas-Gonzalez, N.; Rosales-Hernandez, B.; Estrada-Garcia, I.; Mendez-Aragon, P.; Carranza-Rosales, P.; Gonzalez-Garza, M.T.; Castro-Garza, J. Antimycobacterialactivity of Juglans regia, Juglans mollis, Carya illinoensis and Bocconia frutescens. Phytother. Res. 2008, 22, 557–559. [Google Scholar] [CrossRef]
  57. Wang, B.; Cheng, P.; Chen, J.L.; Zeng, J.G. Extraction of quaternary benzophenanthridine alkaloids (QBAs) from Macleaya cordata and antibacterial activity, acute toxicity of the QBAs bisulfate. Chin. J. Pestic. Sci. 2013, 15, 299–304. [Google Scholar]
  58. Newman, S.E.; Roll, M.J.; Harkrader, R.J. A naturally occurring compound for controlling powdery mildew of greenhouse roses. Hortscience 1999, 34, 686–689. [Google Scholar]
  59. Calzada, F.; Yepez-Mulia, L.; Tapia-Contreras, A. Effect of Mexican medicinal plant used to treat trichomoniasis on Trichomonas vaginalis trophozoites. J. Ethnopharmacol. 2007, 113, 248–251. [Google Scholar] [CrossRef]
  60. Chinchilla, M.; Valerio, I.; Sanchez, R.; Mora, V.; Bagnarello, V.; Martinez, L.; Gonzalez, A.; Vanegas, J.C.; Apestegui, A. In vitro antimalarial activity of extracts of some plants from a biological reserve in Costa Rica. Rev. Biol. Trop. 2012, 60, 881–891. [Google Scholar]
  61. Feng, G.; Zhang, J.; Liu, Y.Q. Inhibitory activity of dihydrosanguinarine and dihydrochelerythrine against phytopathogenic fungi. Nat. Prod. Res. 2011, 25, 1082–1089. [Google Scholar] [CrossRef]
  62. Liu, H.; Wang, J.H.; Zhao, J.L.; Lu, S.Q.; Wang, J.G.; Jiang, W.B.; Ma, Z.H.; Zhou, L.G. Isoquinoline alkaloids from Macleaya cordata active against plant microbial pathogens. Nat. Prod. Commun. 2009, 4, 1557–1560. [Google Scholar]
  63. Vrublova, E.; Vostalova, J.; Ehrmann, J.; Palikova, I.; Vrbkova, J.; Vacek, J.; Cibicek, N.; Vecera, R.; Ulrichova, J.; Simanek, V. The phytogenetic feed additive Sangrovit modulates dextran sulfate sodium-induced colitis in rats. Vet. Med.-Czech 2010, 55, 610–618. [Google Scholar]
  64. Vrba, J.; Orolinova, E.; Ulrichova, J. Induction of heme oxygenase-1 by Macleaya cordata extract and its constituent sanguinarine in RAW264.7 cells. Fitoterapia 2012, 83, 329–335. [Google Scholar] [CrossRef]
  65. Ibarra-Alvarado, C.; Rojas, A.; Mendoza, S.; Bah, M.; Gutierrez, D.M.; Hernandez-Sandoval, L.; Martinez, M. Vasoactive and antioxidant activities of plants used in Mexican traditional medicine for the treatment of cardiovascular diseases. Pharm. Biol. 2010, 48, 732–739. [Google Scholar] [CrossRef]
  66. Caballero-George, C.; Vanderheyden, P.M.L.; Solis, P.N.; Pieters, L.; Shahat, A.A.; Gupta, M.P.; Vauquelin, G.; Vlietinck, A.J. Biological screening of selected medicinal Panamanian plants by radioligand-binding techniques. Phytomedicine 2001, 8, 59–70. [Google Scholar] [CrossRef]
  67. Caballero-George, C.; Vanderheyden, P.M.L.; Solis, P.N.; Gupta, M.P.; Pieters, L.; Vauquelin, G.; Vlietinck, A. In vitro effect of sanguinarine alkaloid on binding of [3H] candesartan to the human angiotensin AT1 receptor. Eur. J. Pharmacol. 2003, 458, 257–262. [Google Scholar] [CrossRef]
  68. Velazquez, C.; Calzada, F.; Torres, J.; Gonzalez, F.; Ceballos, G. Antisecretory activity of plants used to treat gastrointestinal disorders in Mexico. J. Ethnopharmacol. 2006, 103, 66–70. [Google Scholar] [CrossRef]
  69. Yang, J.; Wang, J.; Liu, X.S.; Fang, X.M. Experimental studies on pharmacodynamic effect of Macleaya cordata. Chin. Med. Mat. 1999, 22, 82–85. [Google Scholar]
  70. Kang, H.S.; Chung, H.Y.; Son, K.H.; Kang, S.S.; Choi, J.S. Scavenging effect of Korean medicinal plants on the peroxynitrite and total ROS. Nat. Prod. Sci. 2003, 9, 73–79. [Google Scholar]
  71. Zhong, M.; Huang, K.L.; Zeng, J.G.; Li, S.; Zhang, L. Determination of contents of eight alkaloids in fruits of Macleaya cordata (Willd) R. Br. from different habitats and antioxidant activities of extracts. J. Cent. South Univ. Technol. 2010, 17, 472–479. [Google Scholar] [CrossRef]
  72. Sedo, A.; Vlasicova, K.; Bartak, P.; Vespalec, R.; Vicar, J.; Simanek, V.; Ulrichova, J. Quaternary benzo[c]phenanthridine alkaloids as inhibitors of aminopeptidase N and dipeptidyl peptidase IV. Phytother. Res. 2002, 16, 84–87. [Google Scholar]
  73. Sedo, A.; Malik, R.; Vicar, J.; Simanek, V.; Ulrichova, J. Quaternary benzo[c]phenanthridine alkaloids as inhibitors of dipeptidyl peptidase IV-like activity bearing enzymes in human blood plasma and glioma cell lines. Physiol. Res. 2003, 52, 367–372. [Google Scholar]
  74. Jankowski, J.; Zdunczyk, Z.; Juskiewicz, J.; Kozlowski, K.; Lecewicz, A.; Jeroch, H. Gastrointestinal tract and metabolic response of broilers to diets with the Macleaya cordata alkaloid extract. Arch. Geflugelk. 2009, 73, 95–101. [Google Scholar]
  75. Juskiewicz, J.; Gruzauskas, R.; Zdunczyk, Z.; Semaskaite, A.; Jankowski, J.; Totilas, Z.; Jarule, V.; Sasyte, V.; Zdunczyk, P.; Raceviciute-Stupeliene, A.; et al. Effects of dietary addition of Macleaya cordata alkaloid extract on growth performance, caecal indices and breast meat fatty acids profile in male broilers. J. Anim. Physiol. Anim. Nutr. 2011, 95, 171–178. [Google Scholar] [CrossRef]
  76. Shu, K.G. A report of poisoning by food containing Macleaya cordata. Chin. J. Med. 1980, 11, 23–23. [Google Scholar]
  77. Chen, J.K. Report of a case: Poisoning by Macleaya cordata. Hunan Med. J. 1991, 8, 159. [Google Scholar]
  78. Psotova, J.; Vecera, R.; Zdarilova, A.; Anzenbacherova, E.; Kosina, P.; Svobodova, A.; Hrbac, J.; Jirovsky, D.; Stiborova, M.; Lichnovsky, V.; et al. Safety assessment of sanguiritrin, alkaloid fraction of Macleaya cordata, in rats. Vet. Med.-Czech. 2006, 51, 145–155. [Google Scholar]
  79. Zdunczyk, Z.; Gruzauskas, R.; Juskiewicz, J.; Semaskaite, A.; Jankowski, J.; Godycka-Klos, I.; Jarule, V.; Miezeliene, A.; Alencikiene, G. Growth performance, gastrointestinal tract responses, and meat characteristics of broiler chickens fed a diet containing the natural alkaloid sanguinarine from Macleaya cordata. J. Appl. Poult. Res. 2010, 19, 393–400. [Google Scholar] [CrossRef]
  80. Rawling, M.D.; Merrifield, D.L.; Davies, S.J. Preliminary assessment of dietary supplementation of Sangrovit on red tilapia (Oreochromis niloticus) growth performance and health. Aquaculture 2009, 294, 118–122. [Google Scholar] [CrossRef]
  81. Kosina, P.; Walterova, D.; Ulrichova, J.; Ulrichova, J.; Lichnovsky, V.; Stiborova, M.; Rydlova, H.; Vicar, J.; Krecman, V.; Brabec, M.J.; Simanek, V. Sanguinarine and chelerythrine: assessment of safety on pigs in ninety days feeding experiment. Food Chem. Toxicol. 2004, 42, 85–91. [Google Scholar] [CrossRef]
  82. Vacek, J.; Papoušková, B.; Kosina, P.; Galandáková, A.; Ulrichová, J. Mass spectrometric investigation of chelerythrine and dihydrochelerythrine biotransformation patterns in human hepatocytes. J. Chromatogr. B 2013, 941, 17–24. [Google Scholar] [CrossRef]
  83. Jancula, D.; Suchomelova, J.; Gregor, J.; Smutna, M.; Marsalek, B.; Taborska, E. Effects of aqueous extracts from five species of the family Papaveraceae on selected aquatic organisms. Environ. Toxicol. 2007, 22, 480–486. [Google Scholar] [CrossRef]
  84. Stiborova, M.; Vostalova, J.; Zdarilova, A.; Ulrichova, J.; Hudecek, J.; Tschirner, K.; Simanek, V. Macleaya cordata extract and Sangrovit genotoxicity. Assessment in vivo. Biomed. Pap. 2008, 152, 35–39. [Google Scholar] [CrossRef]
  85. Archambault, J.; Williams, R.D.; Bedard, C.; Chavarie, C. Production of sanguinarine by elicited plant cell culture. I. Shake flask suspension cultures. J. Biotechnol. 1996, 46, 95–105. [Google Scholar] [CrossRef]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top