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.

Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside isolated from the flowers of Hosta plantaginea exerts anti-inflammatory activity via suppression of NF-κB, MAPKs and Akt pathways in RAW 264.7 cells.

Kaempferol 3-O-(2G-glucosylrutinoside)-7-O-glucoside (KGG) has isolated from Hosta plantaginea flowers and possessed an inhibitory effect on cyclooxygenase 2 (COX-2), could be effective in inhibiting inflammation. However, the anti-inflammatory activity and mechanism of KGG remain unknown. In this study, for the first time, the anti-inflammatory effect of KGG and its potential molecular mechanisms were explored in cells. KGG had no cytotoxicity at concentrations of 1.25, 2.5, 5, 10, 20, and 40 µM by Cell Counting kit-8 assay in RAW 264.7 cells. Besides, KGG concentration-dependently (1.25, 2.5, and 5 µM) inhibited secretions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Western blot showed that the phosphorylation of nuclear factor kappa-B (NF-κB) p65, inhibitor of NF-κB (IκB), p38 MAPK, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (Erk), and protein kinase B (Akt), together with inducible nitric oxide synthase (iNOS) and COX-2 were significantly attenuated by KGG (1.25, 2.5, and 5 µM) in a concentration-dependent relationship. Meanwhile, KGG remarkably enhanced the protein expression of IκB. Taken together, KGG may be one of bioactive phytochemicals from H. plantaginea flowers, and be an anti-inflammatory agent via inhibiting NF-κB, mitogen-activated protein kinases (MAPKs), and Akt signaling pathways.

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.

Protection by Hosta ventricosa polysaccharides against oxidative damage induced by t-BHP in HepG2 cells via the JNK/Nrf2 pathway.

Hosta ventricosa is a plant that can be used for medicine and diet. It has been proven to have anti-inflammatory, antibacterial and antitumor activities, and one of its main constituents is polysaccharides. However, studies on polysaccharides of Hosta ventricosa are limited, and their physiological activities have not been clarified. Therefore, isolation, purification and characterization of Hosta ventricosa root polysaccharides (HVRPp-1) were performed in this research. Furthermore, the effect of HVRPp-1 on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells was investigated in vitro. The results showed that HVRPp-1 is a nonhomogeneous polysaccharide that could protect HepG2 cells from oxidative damage through the C-Jun N-terminal kinase (JNK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. In conclusion, this research proved the antioxidant mechanism of HVRPp-1 for the first time, providing a reliable theoretical basis for basic research on Hosta ventricosa polysaccharides and the possibility of their application in functional foods.

Isolation and functional diversification of dihydroflavonol 4-Reductase gene HvDFR from Hosta ventricosa indicate its role in driving anthocyanin accumulation.

Anthocyanins are natural colorants are synthesized in a branch of the flavonoid pathway. Dihydroflavonol-4reductase (DFR) catalyzes dihydroflavonoids into anthocyanins biosynthesis, which is a key regulatory enzyme of anthocyanin biosynthesis in plants. Hosta ventricosa is an ornamental plant with elegant flowers and rich colorful leaves. How the function of HvDFR contributes to the anthocyanins biosynthesis is still unknown. In this study, the DFR homolog was identified from H. ventricosa and sequence analysis showed that HvDFR possessed the conserved NADPH binding and catalytic domains. A phylogenetic analysis showed that HvDFR was close to the clade formed with MaDFR and HoDFR in Asparagaceae. Gene expression analysis revealed that HvDFR was constitutive expressed in all tissues and expressed highly in flower as well as was positively correlated with anthocyanin content. In addition, the subcellular location of HvDFR showed that is in the nucleus and cell membrane. Overexpression of HvDFR in transgenic tobacco lines enhanced the anthocyanins accumulation along with the key genes upregulated, such as F3H, F3'H, ANS, and UFGT. Our results indicated a functional activity of the HvDFR, which provide an insight into the regulation of anthocyanins content in H. ventricosa.

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.

Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves.

Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves.