Amelioration of chronic prostatitis by fractions of Mongolian medicine Hosta plantaginea flowers via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hosta plantaginea (Lam.) Aschers flower is an important Mongolian medicine beneficial in the treatment of chronic prostatitis (CP) in the absence of scientific evidence. AIM OF THE STUDY: The aim of this study was to reveal the therapeutical effects and potential mechanisms of H. plantaginea flowers extract (HP) and its different polarity fractions (HPA∼D) on autoimmune CP (ACP) model rats. MATERIALS AND METHODS: Sprague-Dawley male rats were randomly assigned to 13 groups (n = 6/group). Except the sham group, all rats were injected with a mixture of prostate antigen and complete Freund's adjuvant on days 0, 7, and 21 to establish ACP model rats. Afterwards, ACP model rats were orally gavaged with HP or HPA∼D (1 and 4 g/kg of raw herbal material) or positive drug (Prostat, 200 mg/kg) daily from day 21 to day 50 for 30 days, while the sham and model groups were treated simultaneously with isopyknic of 0.3% sodium carboxymethyl cellulose. Histopathological analysis, biochemical parameters, and protein expression of prostate tissues were investigated. RESULTS: In comparison with the model group, all fraction groups experienced improved CP effects, including restored body weight, reduced prostate gland edema and prostate index, decreased prostatic leukocytes, increased prostatic lecithin bodies, and alleviated histopathological damage to prostate tissue. Furthermore, all fraction groups markedly inhibited the phosphorylated protein of nuclear factor kappa-B p65 (NF-κB p65), NF-κB inhibitor alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) than the model group. CONCLUSION: All fractions of HP exerted significant anti-CP effects by inhibiting NF-κB, MAPKs, JAK-STAT and PI3K-Akt pathways in ACP model rats. These findings provide scientific evidence that H. plantaginea flowers can be used as a pivotal Mongolian medicine in clinical applications for the treatment of CP.

Potential active constituents responsible for treating acute pharyngitis in the flowers of Hosta plantaginea (Lam.) Aschers and their pharmacokinetics.

In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine. The hosta flower is often used as a material for cooking porridge and scented tea and in combination with other plants for alleviating pharyngitis. To clarify the anti-pharyngitis effect of the hosta flower and evaluate its potential active ingredients, an ethanol extract of the hosta flower was prepared and partially purified via chromatography on a column packed with D101 macroporous resin, which was eluted with different concentrations of ethanol. The anti-pharyngitis effect of the crude extract and the various partially purified fractions was examined in an ammonia-induced acute pharyngitis rat model. The 30% ethanol-eluted fraction significantly alleviated the severity of pharyngitis in the rat, as evaluated by changes in the levels of cytokines (IL-1ß, IL-6, and TNF-α) and histological changes in the pharynx tissues. Subsequent HPLC-QTOF/MS (high-performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry) analysis of this fraction revealed kaempferol and its glycosides as the main components. Three of the main components were isolated and identified by 1D NMR. Their pharmacokinetics were studied for the first time by UHPLC-QQQ/MS (ultrahigh-performance liquid chromatography coupled with mass spectrometry). The findings suggested that the 30% ethanol-eluted fraction of the hosta flower extract may be a potential functional food for treating pharyngitis.

Anti-inflammatory effects of flavonoids and phenylethanoid glycosides from Hosta plantaginea flowers in LPS-stimulated RAW 264.7 macrophages through inhibition of the NF-κB signaling pathway.

BACKGROUND: The flower of Hosta plantaginea (Lam.) Aschers has traditionally been used in China as an important Mongolian medicine for the treatment of inflammatory diseases with limited scientific evidence. In previous studies, 16 flavonoids and 3 phenylethanoid glycosides (1-19) were isolated from the ethanolic extract of H. plantaginea flowers. Nevertheless, the anti-inflammatory effects of these constituents remain unclear. In the present study, the anti-inflammatory effects of these 19 constituents and their underlying mechanisms were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. METHODS: The viability of RAW 264.7 macrophages was detected by Cell Counting Kit-8 (CCK-8) assay. Meanwhile, nitric oxide (NO) production was measured by Griess assay, while the secretion of tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), interleukin 1ß (IL-1ß) and IL-6 in LPS-induced macrophages was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, the protein expression of nuclear factor kappa B (NF-κB) p65 and phosphorylated NF-κB p65 was evaluated by Western blot analysis. RESULTS: All constituents effectively suppressed excessive NO production at a concentration of 40 µM with no toxicity to LPS-induced RAW 264.7 macrophages. Among them, five flavonoids (1, 4-6 and 15) and one phenylethanoid glycoside (17) remarkably prevented the overproduction of NO with median inhibitory concentration (IC50) values in the range of 12.20-19.91 µM. Moreover, compounds 1, 4-6, 15 and 17 potently inhibited the secretion of TNF-α, PGE2, IL-1ß and IL-6, and had a prominent inhibitory effect on the down-regulation of the phosphorylated protein level of NF-κB p65. CONCLUSION: Taken together, compounds 1, 4-6, 15 and 17 may be useful in managing inflammatory diseases by blocking the NF-κB signaling pathway and suppressing the overproduction of inflammatory mediators.

Hostaflavone A from Hosta plantaginea (Lam.) Asch. blocked NF-κB/iNOS/COX-2/MAPKs/Akt signaling pathways in LPS-induced RAW 264.7 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Hostaflavone A (HA) is a new flavonoid component isolated from the flower of Hosta plantaginea (Lam.) Asch., which is commonly used as a folk herbal to treat inflammatory diseases in China. Nevertheless, the anti-inflammatory effect of HA remains unknown. AIM OF THE STUDY: This work aimed to evaluate the HA with anti-inflammatory activity and mechanism in RAW 264.7 macrophages activated by lipopolysaccharide (LPS). MATERIALS AND METHODS: Anti-inflammatory effect of HA was evaluated by measuring of cell viability, nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6 levels in RAW 264.7 cells. In parallel, the HA action mechanism of nuclear factor kappa B (NF-κB) p65, inhibitor of NF-κB (IκB), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (Erk), p38, and protein kinase B (Akt) were detected by Western blot analysis. RESULTS: HA has no cytotoxicity at concentrations as high as 40 µM. Besides, HA concentration-dependently clearly suppressed the overproduction of NO, PGE2, TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS. In addition, HA remarkably reduced the upregulation of phosphorylated NF-κB p65, phosphorylated IκB, phosphorylated JNK, phosphorylated Erk and phosphorylated p38, together with iNOS and COX-2 protein expressions in a concentration-dependent manner. CONCLUSION: HA blocked the LPS activated inflammation via suppressing NF-κB, iNOS, COX-2, mitogen-activated protein kinases (MAPKs) and Akt pathways in RAW 264.7 cells, and might be a new anti-inflammatory agent.

Plantanone D, a new rare methyl-flavonoid from the flowers of Hosta plantaginea with anti-inflammatory and antioxidant activities.

Flowers of Hosta plantaginea have been used for the treatment of inflammation-related diseases in traditional Chinese medicine with limited scientific validation. In the present work, we reported one new rare methyl-flavonoid, plantanone D (1) and one known compound 4-hydroxybenzoic acid (2) from the flowers of H. plantaginea. Their structures were elucidated on the basis of chemical and spectral evidence, as well as by comparison with literature data. To the best of our knowledge, the methyl-flavonoid skeleton have not been reported from any species in Liliaceae family, compound 2 was isolated from the genus Hosta for the first time. The anti-inflammatory activities against cyclooxygenases (COX-1 and COX-2) and antioxidant activities in vitro results revealed that 1 exhibited significant COX-1 inhibition and moderate COX-2 inhibition compared to the reference celecoxib. Additionally, 1 displayed significant antioxidant activity compared to the positive control L-ascorbic acid.

Traditional uses, phytochemistry, pharmacology and toxicological aspects of the genus Hosta (Liliaceae): A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hosta (Liliaceae family) represents an interesting source of natural bio-constituents, and the 50 species of this genus are widespread in the world. Five species have been used as traditional East Asian medicines for treating inflammation and pain-related diseases. However, the available data for this genus have not been comprehensively reviewed regarding their extracts and secondary metabolites. AIM OF THE STUDY: The present review aims to provide a deeper insight, better awareness and detailed knowledge of traditional uses, phytochemistry, pharmacology along with toxicological aspects of the genus Hosta in the past decades (February 1964 to August 2020). In addition, the relevance among traditional uses, pharmacology and phytochemistry in folk medicines were extensively discussed. MATERIALS AND METHODS: The relevant information of Hosta species was obtained from several databases. Moreover, the medical books, PhD and MSc dissertations in Chinese were also used to perform this work. RESULTS: Comprehensive analysis of the afore-mentioned databases, medical books and dissertations confirmed that ethnomedical uses of Hosta genus plants had been recorded in China, Japan, Korea and other countries. To date, only eight species have been studied for chemical constituents, and a total of 200 secondary metabolites (not include essential oil constituents), including steroids, flavonoids, alkaloids, furan derivatives, phenylpropanoids, phenethyl derivatives, terpenoids, aliphatics, and others. The crude extracts and isolated chemical constituents exhibited anti-inflammatory and analgesic, antioxidant, anti-tumor, anti-viral, acetylcholinesterase inhibitory, antimicrobial, anti-chronic prostatitis, and other effects. Moreover, only the n-butanol fraction of H. ventricosa (Salisb.) Stearn roots showed moderate acute toxicity in mice. In addition, the relevance among traditional uses, pharmacology and phytochemistry in folk medicines were extensively discussed. CONCLUSIONS: Hosta spp. are plants rich in steroids and flavonoids with valuable medicinal properties; though, there are several gaps in understanding the traditional uses in the current available data. More high scientific quality preclinical studies with new methodology are necessary to assess the safety, efficacy and mechanism of these plants.

Isolation and characterization of flavonoid derivatives with anti-prostate cancer and hepatoprotective activities from the flowers of Hosta plantaginea (Lam.) Aschers.

ETHNOPHARMACOLOGICAL RELEVANCE: The flower of Hosta plantaginea (Lam.) Aschers (Liliaceae) is a traditional medicinal material in Mongolian medicine for treating sore throat, hoarseness, pulmonary fever, and toxic fever in folk. The present work investigated anti-prostate cancer and hepatoprotective activities of flavonoid derivatives from H. plantaginea (Lam.) Aschers. AIM OF THE STUDY: To isolate and identify the chemicals of H. plantaginea (Lam.) Aschers for anti-prostate cancer and hepatoprotective activities. MATERIALS AND METHODS: Active chemicals were isolated and purified from H. plantaginea (Lam.) Aschers by chromatographic methods, and their structures were established on spectroscopic analysis and references. These compounds were evaluated for their anti-prostate cancer activities using the LNCaP prostate cancer cells, and assayed for their hepatoprotective activities on CCl4-induced injury of human L-O2 cells, respectively. RESULTS: Four new flavonol-lignan heterodimers (1-4), together with nine known flavonoid derivatives (5-13) were isolated from this plant for the first time. Among them, some compounds exhibited moderate anti-prostate cancer and hepatoprotective activities. CONCLUSION: Compounds 1, 2, 5, and 6 showed anti-prostate cancer activities using the LNCaP prostate cancer cells with IC50 values of 17.84, 33.26, 54.13, and 81.55 µg/mL, and compounds 3, 4, 8, and 9 exhibited moderate hepatoprotective activities, respectively. A preliminary structure-activity relation was summarized in this paper.

Five new compounds from Hosta plantaginea flowers and their anti-inflammatory activities.

Five new compounds hostines A-E (1-5), together with eighteen known compounds (6-23), were obtained from the flowers of Hosta plantaginea (Lam.) Aschers, a traditional folk herbal medicine widely used in Mongolian. The structures of the undescribed compounds were determined by using detailed spectroscopic (1D/2D NMR) and HR-ESI-MS data analysis. The biological evaluation revealed that hostine C (3), hostine D (4), hostine E (5), stellarine (16), and phenethyl-O-ß-d-glucopuranoside (19) possessed the significant anti-inflammatory activities, these compounds significantly inhibited the NO release of RAW 264.7 cells induced by LPS. The possible mechanism of NO inhibition of new bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.

[A new antioxidant flavonoid glycoside from flowers of Hosta plantaginea].

Phytochemical investigation of the flowers of Hosta plantaginea led to isolate of one new flavonoid glycoside,plantanone C( 1) by silica gel,Sephadex LH-20,and RP-HPLC column chromatographies. Its structure was extensively determined on basis of HR-ESI-MS and NMR spectroscopic data. Compound 1 exhibited moderate antioxidant activity against DPPH radical scavenging activity,with an IC50 value of 240. 2 µmol·L~(-1).

A new flavonol glycoside from the flowers of Hosta plantaginea with cyclooxygenases-1/2 inhibitory and antioxidant activities.

Hosta plantaginea was a traditional Chinese medicinal plants used to treat inflammatory and painful diseases with partial scientific validation. Solvent extractions followed by repeated chromatographic purification of the H. plantaginea flowers led to the isolation of one new flavonoid glycoside, hostaflavone A (1), together with one related known compound, kaempferol-3-O-sophoroside-7-O-glucoside (2), and their structures were elucidated on the basis of chemical and spectral evidence, as well as by comparison with literature data. Compounds 1 and 2 were evaluated for the anti-inflammatory activites against cyclooxygenases (COX-1 and COX-2) and DPPH free radical-scavenging activities in vitro. The results revealed that 1 and 2 exhibited significant COX-1 inhibition and moderate COX-2 inhibition compared to the reference celecoxib. Additionally, 1 and 2 displayed insignificant antioxidant activities compared to the positive control L-ascorbic acid.

Chemical Constituents from the Flower of Hosta plantaginea with Cyclooxygenases Inhibition and Antioxidant Activities and Their Chemotaxonomic Significance.

Two new phenolic glucosides, hostaflavanone A (1) and anti-1-phenylpropane-1,2-diol-2-O-ß-d-glucopyranoside (2), together with six known compounds, anti-1-phenylpropane-1,2-diol (3), phenethyl-O-ß-d-glucopyranoside (4), phenethanol-ß-d-gentiobioside (5), phenethyl-O-rutinoside (6), (1S, 3S)-1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (7), and (1R, 3S)-1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (8), were isolated from the flower of Hosta plantaginea, and their structures were elucidated by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), and circular dichroism (CD) analyses. The cyclooxygenases (COX-1 and COX-2) inhibition and antioxidant activities of compounds 1 and 4-6 were investigated, and they showed moderate cyclooxygenases inhibition activities. Moreover, only compound 1 exhibited moderate antioxidant activity, with an IC50 value of 83.2 µM, while 4-6 showed insignificant activity with IC50 values of 282, 257, and 275 µM, respectively. This is the first report of compounds 3 and 5-8 from the Liliaceae family. The chemotaxonomic significance of the isolated compounds was also summarized.

New steroidal glycosides from Hosta plantaginea (Lam.) Aschers.

Four new furostanol glycosides were isolated from the flowers of Hosta plantaginea (Lam.) Aschers. On the basis of spectroscopic methods including 1D and 2D NMR experiments, their structures were elucidated as 26-O-ß-d-glucopyranosyl-(25R)-22-O-methyl-5α-furostan-2α,3ß,22ξ,26-tetrol 3-O-α-l-rhamnopyranosyl-(1 â†’ 4)-O-ß-d-xylopyranosyl-(1 â†’ 3)-[O-ß-d-glucopyranosyl-(1 â†’ 2)]-O-ß-d-glucopyranosyl-(1 â†’ 4)-ß-d-galactopyranoside (hostaplantagineoside A, 1), 26-O-ß-d-glucopyranosyl-(25R)-5α-furostan-20(22)-ene-2α,3ß,26-triol-3-O-ß-d-glucopyranosyl-(1 â†’ 2)-[O-ß-d-xylopyranosyl-(1 â†’ 3)]-O-ß-d-glucopyranosyl-(1 â†’ 4)-ß-d-galactopyranoside (hostaplantagineoside B, 2), 26-O-ß-d-glucopyranosyl-(25R)-5α-furostan-22(23)-ene-2α,3ß,20α,26-tetraol-3-O-ß-d-glucopyranosyl-(1 â†’ 2)-[O-ß-d-xylopyranosyl-(1 â†’ 3)]-O-ß-d-glucopyranosyl-(1 â†’ 4)-O-ß-d-galactopyranoside (hostaplantagineoside C, 3), 26-O-ß-d-glucopyranosyl-(25R)-5α-furostan-20(22)-ene-2α,3ß,26-triol-3-O-α-l-rhamnopyranosyl-(1 â†’ 4)-O-ß-d-xylopyranosyl-(1 â†’ 3)-[O-ß-d-glucopyranosyl-(1 â†’ 2)]-O-ß-d-glucopyranosyl-(1 â†’ 4)-ß-d-galactopyranoside (hostaplantagineoside D, 4).

The relative importance of architecture and resource competition in allocation to pollen and ovule number within inflorescences of Hosta ventricosa varies with the resource pools.

BACKGROUND AND AIMS: Allocation of resources to floral traits often declines distally within inflorescences in flowering plants. Architecture and resource competition have been proposed as underlying mechanisms. The aim of the present study is to assess the relative importance of resource competition and architectural effects in pollen and ovule production on racemes of Hosta ventricosa, an apomictic perennial herb. METHODS: Combinations of two defoliation treatments (intact and defoliated) and two fruit-set treatments (no-fruit and fruit) were created, and the roles of architecture and resource competition at each resource level were assessed. KEY RESULTS: Pollen and ovule number per flower increased after defoliation, but pollen to ovule ratio per flower did not change. Pollen, ovules and the pollen to ovule ratio per flower declined distally on racemes at each resource level. In the intact treatment, fruit development of early flowers did not affect either pollen or ovule number of late flowers. In the defoliated treatment, fruit development of early flowers reduced both pollen and ovule numbers of late flowers due to over-compensation caused by defoliation. Late flowers on defoliated fruit racemes produced less pollen than intact fruit racemes but the same number of ovules; therefore, the reduction in pollen number was not caused by over-compensation. In addition, the fruit-set rate of early flowers during flowering was higher in intact racemes than in defoliated racemes. CONCLUSIONS: In flowering plants, the relative importance of architecture and resource competition in allocation to pollen and ovules may vary with the resource pools or the overall resource availability of maternal plants.

Benzylphenethylamine alkaloids from Hosta plantaginea with inhibitory activity against tobacco mosaic virus and acetylcholinesterase.

Five new benzylphenethylamine alkaloids, hostasine (1), 8-demethoxyhostasine, 8-demethoxy-10-O-methylhostasine, 10-O-methylhostasine, and 9-O-demethyl-7-O-methyllycorenine, along with 12 known compounds, were isolated from Hosta plantaginea by bioassay-guided fractionation. The structures of the new alkaloids were established by means of extensive spectroscopic methods, and the relative configuration of 1 was further confirmed by single-crystal X-ray diffraction. 7-Deoxy-trans-dihydronarciclasine (IC(50) = 1.80 microM), a known alkaloid, showed strong activity against tobacco mosaic virus by the half-leaf method. Some of these alkaloids were also evaluated for their inhibitory activity against acetylcholinesterase. 8-Demethoxy-10-O-methylhostasine was found to possess significant activity, with an IC(50) of 2.32 microM.

[Pharmacognostical identification of "guijiu ([symbol: see text])" in Shosoin of Japan].

OBJECTIVE: To identify the botanical origin of the Guijiu in Shosoin of Japan from Tang Dynasty, and trace its medicinal history. METHOD: Anatomical characteristics of the underground parts of Guijiu in Shosoin were compared with those of Hosta plantaginea and H. ventricosa, and research on the medicinal history of Guijiu was made based on its original identification results and describes in herbals. RESULT AND CONCLUSION: Guijiu in Shosoin of Japan was derived from the underground parts of H. plantaginea and is one of Guijiu used in Tang Dynasty and earlier on.

Pharmacognostical identification of "guijiu (symbol: see text)" in Shosoin of Japan / 中国中药杂志

<p><b>OBJECTIVE</b>To identify the botanical origin of the Guijiu in Shosoin of Japan from Tang Dynasty, and trace its medicinal history.</p><p><b>METHOD</b>Anatomical characteristics of the underground parts of Guijiu in Shosoin were compared with those of Hosta plantaginea and H. ventricosa, and research on the medicinal history of Guijiu was made based on its original identification results and describes in herbals.</p><p><b>RESULT AND CONCLUSION</b>Guijiu in Shosoin of Japan was derived from the underground parts of H. plantaginea and is one of Guijiu used in Tang Dynasty and earlier on.</p>