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Copyright of Journal of Henan Agricultural Sciences is the property of Editorial Board of Journal of Henan Agricultural Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In vitro single‐cell experiments may yield inconsistent results compared to clinical trials. To enhance the reliability of cosmetic active ingredient screening, a coculture model of B16F10‐HaCaT cells was established in vitro based on the structural characteristics of human skin, thereby improving the credibility of experimental outcomes. Currently, most cosmetic whitening additives primarily target simple efficacy goals such as inhibiting tyrosinase activity or melanin transfer. Therefore, investigating novel and efficient whitening additives has become a prominent research focus. Objectives: The aim is to establish an in vitro cell coculture model for more reliable experimental results and investigate the mechanism by which Paeonia lactiflora Pall seeds oil inhibits melanin production and transfer. Methods: The impact of different concentrations of Paeonia lactiflora Pall seeds oil on cocultured cell proliferation rate was assessed using cck8 assay. Tyrosinase inhibition ability in cocultured cells was tested using levodopa as a substrate. Melanin production inhibition ability in coculture cells was evaluated by lysing cells with sodium hydroxide. The effect of Paeonia lactiflora Pall seeds oil on dendrite‐related gene expression levels was examined through qPCR analysis. Additionally, Western blotting was employed to study the effect of Paeonia lactiflora Pall seeds oil on dendrite‐related protein expression levels. Results: Different concentrations of Paeonia lactiflora Pall seeds oil did not affect the proliferation activity of cocultured cells. A specific concentration of α‐MSH increased cell tyrosinase activity, cellular melanin content, as well as Rac1, Cdc42, and PAR‐2 gene and protein expression related to dendritic formation. Treatment with a certain concentration of Paeonia lactiflora Pall seeds oil resulted in decreased tyrosinase activity and melanin content in cells along with downregulated expression levels of Rac1, Cdc42, and PAR‐2 genes and proteins associated with dendritic formation. Conclusions: Paeonia lactiflora Pall seeds oil at specific concentrations exhibits the ability to inhibit tyrosinase activity, decrease melanin content, and possesses the potential to impede melanin transfer. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant (p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein–protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pall. is widely used in medicine, garden applications, and as a potted ornamental. Cultivated varieties of paeonifloras suitable for cut flowers are urgently needed. In this study, the pollen morphology of P. lactiflora was studied and the characters of different varieties were compared, so as to provide reference for selecting suitable parents for new hybrid varieties. We examined the pollen morphology of 15 herbaceous peony varieties using scanning electron microscopy and analyzed the external pollen morphology and genetic relationship of the varieties. The pollen grains of the studied varieties were spheroidal or subspheroidal, bilaterally symmetrical monads, circular in polar view, and circular or elliptical in equatorial view. The exine of the pollen grains was observed as being relatively smooth under the light microscope, with the area around the equatorial axis having more lumina under the scanning electron microscope. The pollen grain exine sculpture was either reticular or pit type. The pollen apertures were tricolporate, arranged longitudinally, and equally spaced. The pollen grains were of two sizes: medium and small. The differences between the varieties were mainly reflected in the exine sculpture of the pollen. The closer the genetic relationship between the 15 peony varieties, the more subtle the differences in the exine sculpture. In the same cluster group, the morphological characteristics of herbaceous peony pollen were correlated with the shapes of flower and scale buds and the texture of the petals. However, the study identified no direct correlation with the cultivar type and flower color. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pall., one of the most famous classical herbal medicine, has been used to treat diseases for over 1200 years. In this research, the functional ingredients were purified by online‐switch two‐dimensional high‐speed counter‐current chromatography combined with inner‐recycling and continuous injection mode. The antioxidant activity was evaluated by investigating the 2,2′‐azobis (2‐amidinopropane) dihydrochloride‐induced oxidant damage in vitro and confirmed through molecular docking. n‐Butanol/ethyl acetate/water (2:3:5, v/v) solvent system was used for the first‐dimensional separation and optimized the sample loading. Two pure compounds and a polyphenol‐enriched fraction were separated. The polyphenol‐enriched fraction was separated with a solvent system n‐hexane/ethyl acetate/methanol/water (2:8:4:6, v/v) with continuous injection mode. Five compounds were successfully separated, including gallic acid (1), methyl gallate (2), albiflorin (3), paeoniflorin (4), and ethyl gallate (5). Their structures were identified by mass spectrometry and NMR spectroscopy. The results from the antioxidant effect showed that albiflorin had stronger antioxidant activity. Molecular docking results indicated that the affinity energy of the identified compounds ranged from ‐3.79 to ‐8.22 kcal/mol and albiflorin showed the lowest affinity energy. Overall, all those findings suggested that the strong antioxidant capacity of albiflorin can be potentially used for the treatment of diseases caused by oxidation. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pall. is widely used in medicine, garden applications, and as a potted ornamental. Cultivated varieties of paeonifloras suitable for cut flowers are urgently needed. In this study, the pollen morphology of P. lactiflora was studied and the characters of different varieties were compared, so as to provide reference for selecting suitable parents for new hybrid varieties. We examined the pollen morphology of 15 herbaceous peony varieties using scanning electron microscopy and analyzed the external pollen morphology and genetic relationship of the varieties. The pollen grains of the studied varieties were spheroidal or subspheroidal, bilaterally symmetrical monads, circular in polar view, and circular or elliptical in equatorial view. The exine of the pollen grains was observed as being relatively smooth under the light microscope, with the area around the equatorial axis having more lumina under the scanning electron microscope. The pollen grain exine sculpture was either reticular or pit type. The pollen apertures were tricolporate, arranged longitudinally, and equally spaced. The pollen grains were of two sizes: medium and small. The differences between the varieties were mainly reflected in the exine sculpture of the pollen. The closer the genetic relationship between the 15 peony varieties, the more subtle the differences in the exine sculpture. In the same cluster group, the morphological characteristics of herbaceous peony pollen were correlated with the shapes of flower and scale buds and the texture of the petals. However, the study identified no direct correlation with the cultivar type and flower color.

A new C6-C2 dimer phenol derivative, colletodiphenol A (1), along with two known C6-C2 phenol derivatives (2,3) were isolated from the endophytic fungus Colletotrichum capsici related to the traditional Chinese medicine Paeonia lactiflora. Their structures were elucidated based on extensive spectroscopic data analysis, including HRESIMS, UV, IR, 1D and 2D NMR. The antioxidant and anti-inflammatory activities of the isolated compounds were evaluated, but none of them displayed significant activity. [ABSTRACT FROM AUTHOR]

The effect of 4-O-galloylalbiflorin on the activity of cytochrome P450 enzymes (CYP450s) is an important factor that may induce drug-drug interaction. The effect of 4-O-galloylalbiflorin on the activity of CYP450s was evaluated in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM 4-O-galloylalbiflorin in pooled human liver microsomes. The inhibition model and corresponding parameters were assessed b fitting with Lineweaver-Burk plots. The time-dependent study was performed with the incubation time of 0, 5, 10, 15, and 30 min. 4-O-galloylalbiflorin significantly inhibited the activity of CYP3A, 2C9, and 2 D in a concentration-dependent manner with the IC50 values of 8.2, 13, and 11 μM, respectively. The inhibition of CYP3A was found to be non-competitive and time-dependent with the Ki value of 4.0 μM and the KI/Kinact value of 2.2/0.030 (μM·min). The inhibition of CYP2C9 and 2 D was not affected by the incubation time but was found to be competitive with the Ki values of 6.7 and 6.6 μM, respectively. The inhibitory effect of 4-O-galloylalbiflorin on the activity of CYP3A, 2C9, and 2 D implying the potential drug-drug interaction between 4-O-galloylalbiflorin and the drugs metabolized by these CYP450s. [ABSTRACT FROM AUTHOR]

Background: Paeoniflorin and liquiritin are the primary active components of Shaoyao-Gancao-tang (SGT), a classical prescription for reducing pains. However, the interaction of paeoniflorin and liquiritin during intestinal absorption needs to be further studied. Objectives: In this study, we aimed to determine the interaction of paeoniflorin and liquiritin during intestinal absorption. Materials and Methods: The interaction between paeoniflorin and liquiritin (100 μM) was studied using in situ single-pass intestinal perfusion (SPIP) model use the whole small intestine and in vitro Caco-2 cell monolayer bidirectional transport model. Results: In situ SPIP research demonstrated that liquiritin significantly increased the Ka, Papp, absorption rate, and cumulative amount of paeoniflorin up to 7.97, 8.98, 7.07, and 10.71 folds, respectively, even higher than that of verapamil, a specific P-gp inhibitor, and control. Furthermore, 18 β-glycyrrhetinic acid (18 β-GA) markedly increased the Ka, Papp, absorption rate, and cumulative amount of paeoniflorin up to 3.30, 3.27, 3.42, and 4.04 folds, respectively. Bidirectional transport studies indicated that liquiritin and paeoniflorin could prompt the absorption of each other by increasing the Papp(AP-BL) of paeoniflorin and liquiritin from (3.83 ± 0.51) ×10−7 to (5.60 ± 0.51) ×10−7 cm/s and (3.86 ± 0.34) ×10−7 to (8.26 ± 0.51) ×10−7 cm/s, respectively. The 18 β-GA significantly prompted the Papp(AP-BL) of paeoniflorin to (5.54 ± 0.92) ×10−7 cm/s. Conclusion: Liquiritin and paeoniflorin increased the absorption of each other. This could provide essential reference to predict the oral bioavailability, the pharmacokinetics, and the clinical application of coadministration of liquiritin-and paeoniflorin-containing SGT and other herbal formulas. [ABSTRACT FROM AUTHOR]

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 μg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 μg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 μg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 μg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

The herbaceous peony (Paeonia lactiflora Pall.) is a perennial flowering plant of the Paeoniaceae species that is widely cultivated for medical and ornamental uses. The monoterpene glucoside paeoniflorin and its derivatives are the active compounds of the P. lactiflora roots. However, the gene regulation pathways associated with monoterpene and paeoniflorin biosynthesis in P. lactiflora are still unclear. Here, we selected three genotypes of P. lactiflora with distinct morphologic features and chemical compositions that were a result of long-term reproductive isolation. We performed an RNA-sequencing experiment to profile the transcriptome changes of the shoots and roots. Using de novo assembly analysis, we identified 36,264 unigenes, including 521 genes responsible for encoding transcription factors. We also identified 28,925 unigenes that were differentially expressed in different organs and/or genotypes. Pathway enrichment analysis showed that the P. lactiflora unigenes were significantly overrepresented in several secondary metabolite biosynthesis pathways. We identified and profiled 33 genes responsible for encoding the enzymescontrolling the major catalytic reactions in the terpenoid backbone and in monoterpenoid biosynthesis. Our study identified the candidate genes in the terpenoid biosynthesis pathways, providing useful information for metabolic engineering of P. lactiflora intended for pharmaceutical uses and facilitating the development of strategies to improve marker-assist P. lactiflora in the future.

Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings.

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 μg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 μg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 μg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 μg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules. [ABSTRACT FROM AUTHOR]

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the formation of β-amyloid peptides (Aβ), which are important in the development of Alzheimer's disease. It has been demonstrated that albiflorin can alleviate Aβ aggregation. However, the mechanism behind this effect is unknown. In our previous work, albiflorin and its four analogues were isolated from Paeonia lactiflora Pall. This study aims to investigate the relationship of these four compounds with BACE1. Our results show that the albiflorin analogue 4-O-galloylalbiflorin (4-O-GA) had the strongest BACE1 inhibitory effect and was also selective for BACE1. Furthermore, docking study of BACE1 with these analogues yielded similar results, whereby 4-O-GA treatment caused the greatest decreases in both the generation of Aβ1–42 and Aβ1–40 and in the expression of BACE1 and HIF-1α. Our findings indicate that 4-O-GA exerted significant and selective inhibitory activities against BACE1, potentially providing a useful agent for developing BACE1 inhibitor drugs.

Background Regulatory T (Treg) cells and T helper 17 (Th17) cells play crucial roles in ulcerative colitis (UC). Kuijieling (KJL) is an effective Chinese medicine formula for treating UC in clinic. Kuijieling has shown remedy effect on the imbalance between Treg and Th17 cells. This study aimed to further reveal the exact underlying mechanism of how Kuijieling regulates the differentiation of Treg and Th17 cells in the treatment of UC. Methods Colitis was induced by trinitrobenzene sulfonic acid in rats and treated by KJL. Pathological injury was evaluated by HE staining and pathological score. Transforming growth factor-β1 (TGF-β1), interleukin(IL)-2, IL-6, IL-10, IL-17, IL-23 and IL-21 in plasma were assayed by ELISA. Forkhead box P3 (Foxp3), signal transducer and activator of transcription (STAT) 5 expressed in colon mucosa were measured by western blot. Immunohistochemistry was employed for quantifying retinoic acid-related orphan receptor γt (RORγt) and STAT3 in colon. RT-PCR was used to analyze the expression of IL-2, IL-17, IL-23, IL-21 mRNA in colon. Results After the administration of KJL, pathological injury in colon mucosa was reduced and histological score was decreased, transforming growth factor-β1 (TGF-β1), interleukin(IL)-2, IL-10 in blood and Foxp3, STAT5, IL-2 in colon increased significantly, IL-6, IL-23, IL-17, IL-21 in blood and RORγt, STAT3, IL-23, IL-17, IL-21 in colon decreased. Our result showed that KJL regulates the related cytokines and transcription factors to promote Treg cells and suppress Th17 cells. Conclusion KJL restores the balance between Treg and Th17 cells through regulating the differentiation of them, therefore contributes to the treatment of UC. [ABSTRACT FROM AUTHOR]

Copyright of Forest Research is the property of Forest Research Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bai Shao (BS, the root of Paeonia lactiflora Pall.), a common Chinese herb in many recipes used to treat viral infection and liver diseases, is recognized for its ability to nourish menstruation, its Yin convergence, and as an antiperspirant. However, the mechanism and components for its antiviral function remain to be elucidated. In this study, an ethanolic extract of BS was further partitioned into aqueous and organic parts (EAex) for in vitro functional study and in vivo efficacy testing. EAex exhibited an IC50 of 0.016 ± 0.005 mg/mL against influenza virus A/WSN/33 (H1N1), with broad-spectrum inhibitory activity against different strains of human influenza A viruses, including clinical oseltamivir-resistant isolates and an H1N1pdm strain. The synthesis of both viral RNA and protein was profoundly inhibited when the cells were treated with EAex. A time-of-addition assay demonstrated that EAex exerted its antiviral activity at various stages of the virus replication cycle. We addressed its antiviral activity at virus entry and demonstrated that EAex inhibits viral hemagglutination and viral binding to and penetration into host cells. In vivo animal testing showed that 200 mg/kg/d of EAex offered significant protection against viral infection. We conclude that BS possesses antiviral activity and has the potential for development as an anti-influenza agent.

The aims of this work were to obtain total glucosides of paeony (TGP) with high content of paeoniflorin and evaluate the hepo-protective properties of TGP. After optimization by response surface methodology, optimized conditions were as follows: extraction time 33.0 min, extraction temperature 48 °C, ethanol content 44%, and the yield of TGP was 47.68 mg/g. Moreover, under established macroporous resin purification, paeoniflorin content of TGP achieved 67.6% in 1.5 L scale-up verification experiment. Purified TGP (p-TGP) was further analyzed by UHPLC-Q-Orbitrap-MS/MS, and 35 compouds including paeoniflorin were identified. The obtained p-TGP effectively reduced biochemical indexes and inflammatory cytokines in liver tissue of acute alcoholic liver injury mice model. Depending on this work, TGP with definitive compound composition exhibited great protective effect against acute alcoholic liver injury in vivo. Furthermore, the finding of this work will be helpful to understand the relationship between compound composition and functional properties of Chinese herb extracts. • Response surface methodology was used to optimize extraction condition of TGP. • Paeoniflorin in TGP was enriched to 67.3% in 1.5 L scale-up DM-2 resin purification. • UHPLC-Q-Orbitrap-MS/MS identified 35 compound in purified TGP. • Purified TGP had great protective effect against acute alcoholic liver injury in vivo. [ABSTRACT FROM AUTHOR]

The roots of Paeonia lactiflora Pall., (Paeoniae Radix, PL) are a well-known herbal remedy used to treat fever, rheumatoid arthritis, systemic lupus erythematosus, hepatitis, and gynecological disorders in East Asia. Here we evaluated the genetic toxicity of PL extracts (as a powder [PL-P] and hot-water extract [PL-W]) in accordance with the Organization for Economic Co-operation and Development guidelines. The Ames test revealed that PL-W was not toxic to S. typhimurium strains and E. coli in absence and presence of the S9 metabolic activation system at concentrations up to 5000 μg/plate, but PL-P produced a mutagenic response to TA100 in the absence of S9 mix. PL-P was cytotoxic in in vitro chromosomal aberrations (more than a 50 % decrease in cell population doubling time), and it increased the frequency of structural and numerical aberrations in absence and presence of S9 mix in a concentration-dependent manner. PL-W was cytotoxic in the in vitro chromosomal aberration tests (more than a 50 % decrease in cell population doubling time) only in the absence of S9 mix, and it induced structural aberrations only in the presence of S9 mix. PL-P and PL-W did not produce toxic response during the in vivo micronucleus test after oral administration to ICR mice and did not induce positive results in the in vivo Pig-a gene mutation and comet assays after oral administration to SD rats. Although PL-P showed genotoxic in two in vitro tests, the results from physiologically relevant in vivo Pig-a gene mutation and comet assays illustrated that PL-P and PL-W does not cause genotoxic effects in rodents. • Paeonia lactiflora Pall (PL) extracts were evaluated in in vitro and in vivo genetic toxicity tests. • Treatment with PL-powder resulted in positive Ames test. • Treatment with PL-powder and PL-hot-water resulted in positive in vitro CA test. • No evidence of in vivo assay (Micronucleus, comet assay, and Pig-a gene mutation) induction with PL extracts. [ABSTRACT FROM AUTHOR]

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the formation of β-amyloid peptides (Aβ), which are important in the development of Alzheimer's disease. It has been demonstrated that albiflorin can alleviate Aβ aggregation. However, the mechanism behind this effect is unknown. In our previous work, albiflorin and its four analogues were isolated from Paeonia lactiflora Pall. This study aims to investigate the relationship of these four compounds with BACE1. Our results show that the albiflorin analogue 4-O-galloylalbiflorin (4-O-GA) had the strongest BACE1 inhibitory effect and was also selective for BACE1. Furthermore, docking study of BACE1 with these analogues yielded similar results, whereby 4-O-GA treatment caused the greatest decreases in both the generation of Aβ 1–42 and Aβ 1–40 and in the expression of BACE1 and HIF-1α. Our findings indicate that 4-O-GA exerted significant and selective inhibitory activities against BACE1, potentially providing a useful agent for developing BACE1 inhibitor drugs. [ABSTRACT FROM AUTHOR]

Flower fragrance not only plays an important role for reproduction of ornamental plants, but also improves the aesthetic value of cut flowers and potted plants, the quality of flower products and their economic value. In this study, the floral headspace compounds of different herbaceous peony cultivars were isolated by a headspace solid-phase microextraction, and followed by gas chromatography-mass spectrometry for identification and quantification. Up to 34 volatile compounds were identified from the 21 herbaceous peony cultivars, including 14 terpenes, 9 alcohols, 7 esters, 1 aldehydes, 1 ketones and 2 arenes. Terpenes, alcohols and esters were the major headspace compounds, whereas the main floral constituents identified in herbaceous peony were caryophyllene, β-citronellol and cinnamic acid methyl ester.Paeonia lactiflora‘Zi Rong Xi Yao’,Paeonia lactiflora‘Mo Zi Han Jin’,Paeonia lactiflora‘Zi Yu Lian’ andPaeonia lactiflora‘Xi Xia Ying Xue’ had a high total amount of β-citronellol, geraniol, phenylethyl alcohol, nerol and their acetate esters, which were also the major headspace compounds of rose (Rosa rugosaThunb.), so they could be considered good materials for improving herbaceous peony fragrance and breeding new cultivars with rose-like fragrance. [ABSTRACT FROM AUTHOR]

A new method for the extraction of medicinal herbs termed ultrasonic-assisted dynamic extraction (UADE) was designed and evaluated. This technique was coupled with counter-current chromatography (CCC) and centrifugal partition chromatography (CPC) and then applied to the continuous extraction and online isolation of chemical constituents from Paeonia lactiflora Pall (white peony) roots. The mechanical parameters, including the pitch and diameter of the shaft, were optimized by means of mathematical modeling. Furthermore, the configuration and mechanism of online UADE coupled with CCC and CPC were elaborated. The stationary phases of the two-phase solvent systems from CCC and CPC were utilized as the UADE solution. The extraction solution was pumped into the sample loop and then introduced into the CCC column; the target compounds were eluted with the lower aqueous phase of the two-phase solvent system. During the CCC separation, the extraction solution was continuously fed in the sample loop by turning the ten-port valve; the extraction solution was then pumped into the CPC column and eluted by the mobile phase of the two-phase solvent system mentioned above. When the first cycle of the UADE/CCC/CPC was completed, the second cycle experiment could be carried out, and so on. Four target compounds (albiflorin, benzoylpaeoniflorin, paeoniflorin, and galloylpaeoniflorin) with purities above 94.96% were successfully extracted and isolated online using the two-phase solvent system comprising ethyl acetate– n -butanol–ethanol–water (1:3.5:2:4.5, v/v/v/v). Compared with conventional extraction methods, the instrumental setup of the present method offers the advantages of automation and systematic extraction and isolation of natural products. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is second only to Alzheimer’s disease as the most common devastating human neurodegenerative disorder. Despite intense investigation, no curative therapy is available for PD. Paeoniflorin, a monoterpene glucoside isolated from the Paeonia lactiflora Pall., possesses wide pharmacological effects in the nervous system. This study aims at evaluating the effect of paeoniflorin on 6-hydroxydopamine (6-OHDA)-induced apoptosis and to characterize involved signal transduction pathways in PC12 cells. Our results showed that paeoniflorin suppresses mitochondria-mediated apoptosis of PC12 cells induced by 6-OHDA, and anti-apoptotic effects of paeoniflorin on PC12 cells might mainly result from its antioxidant capability by increasing glutathione (GSH). Moreover, we also found that paeoniflorin can dramatically attenuate the 6-OHDA-induced nuclear factor κB (NF-κB) translocation without affecting phosphorylation of Akt, JNK, p38, and ERK1/2. 6-OHDA-induced protein kinase Cδ (PKCδ) upregulation was blocked by paeoniflorin treatment in PC12 cells. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium or NF-κB inhibitor BAY 11-7082 could partially attenuate 6-OHDA-induced cell death. Together, our results indicate that the inhibition of PC12 cell apoptosis by paeoniflorin might be mediated, at least in part, by inhibiting reactive oxygen species (ROS)/PKCδ/NF-κB signaling pathway. This evidence supports the pharmacological potential of paeoniflorin in the management of neurodegenerative disorders associated with oxidative stress, including PD. [ABSTRACT FROM AUTHOR]

The article presents a study on the efficacy of paeonol in inflammation-mediated neurotoxity and microglial cell activation. The study employs the application of lipopolysaccharide, nitrite assay, and cell viability assay. Results reveal that paeonol was effective in suppressing nitric oxide release from microglial cells and it reduced the lipopolysaccharide-stimulated release of tumor necrosis factor-alpha.

Abstract: Ethnopharmacological relevance: Radix Paeoniae Rubra (RPR) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China. RPR is the radix of either Paeonia lactiflora Pall. or Paeonia veitchii Lynch. RPR has a wide variety of pharmacological actions such as anti-thrombus, anti-coagulation, and anti-atherosclerotic properties, protecting heart and liver. However, the mechanisms involved are to be defined. Aim of the study: The aim of the present study was to define the effect of Paeonia lactiflora Pall. extracts on vascular tension and responsible mechanisms in rat thoracic aortic rings. Materials and methods: Ethanol extract of Paeonia lactiflora Pall. (EPL) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta. Results: EPL induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Vascular relaxation induced by EPL was significantly inhibited by removal of the endothelium or pretreatment of the rings with NG-nitro-l-arginine methylester (l-NAME) or 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ). Extracellular Ca2+ depletion or diltiazem significantly attenuated EPL-induced vasorelaxation. Modulators of the store-operated Ca2+ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate and Gd3+, and an inhibitor of Akt, wortmannin, markedly attenuated the EPL-induced vasorelaxation. Further, the EPL-induced vasorelaxation was significantly attenuated by pretreatment with tetraethylammonium, a non-selective KCa channels blocker, or glibenclamide, an ATP-sensitive K+ channels inhibitor, respectively. Inhibition of cyclooxygenases with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the EPL-induced vasorelaxation. Conclusions: The present study suggests that EPL relaxes vascular smooth muscle via endothelium-dependent and Akt- and SOCE-eNOS-cGMP-mediated pathways through activation of both KCa and KATP channels and inhibition of L-type Ca2+ channels. [Copyright &y& Elsevier]

Two new monoterpene glucosides, 4'-O-benzoylpaeoniflorin (1) and 4-O-galloylalbiflorin (2), were isolated from the 60% ethanol extract of the dried roots of Paeonia lactiflora Pall. Their structures were established on the basis of spectroscopic data. [ABSTRACT FROM AUTHOR]

The article presents a study to examine the antioxidative and neuroprotective effects of Paeonia lactiflora pall (PLE) on hydrogen peroxide-induced apoptosis in PC12 cells. As part of the study, 435 varieties of herbal medicines were screened. The result showed that PLE could ameliorate induced oxidative stress and apoptosis, and notes the potential therapeutic benefit of PLE in treating neuropathological condition.

A reversed phase high performance liquid chromatography method was established for the simultaneous determination of eight major constituents, namely gallic acid, paeoniflorin sulfonate, catechin, albiflorin, paeoniflorin, benzoic acid, pentagalloylglucose and benzoylpaeoniflorin in red and white peony roots, the two commonly used traditional Chinese medicinal herbs. The optimal conditions of separation and detection were achieved on a C18 analytical column with a gradient mobile phase consisting of acetonitrile and 0.015% phosphoric acid at the flow rate of 1.0 mL min−1 and detection wavelength set at 230 nm. All calibration curves showed good linear regression (r>0.9995) within test ranges. This method provided good reproducibility with overall intra-and inter-day precision of less than 5% and 4% and good accuracy with recovery of more than 93%, respectively. The method was successfully applied to determine 71 samples of red and white peony roots collected from different areas. The results indicated that the contents of eight compounds varied significantly among the samples determined, which mainly resulted from processing procedure and habitat variation. The roots of Paeonia veitchii Lynch. contained a much higher amount of gallic acid and pentagalloylglucose than that of Paeonia lactiflora Pall., which could be used to distinguish the two similar species. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings. [ABSTRACT FROM AUTHOR]

The introduction of herbaceous peony (Paeonia lactiflora Pall.) in low-latitude areas is of great significance to expand the landscape application of this world-famous ornamental. With the hazards of climate warming, warm winters occurs frequently, which makes many excellent northern herbaceous peony cultivars unable to meet their chilling requirements (CR) and leads to their poor growth and flowering in southern China. Exploring the endodormancy release mechanism of underground buds is crucial for improving low-CR cultivar screening and breeding. A systematic study was conducted on P. lactiflora 'Meiju', a screened cultivar with a typical low-CR trait introduced from northern China, at the morphological, physiological and molecular levels. The CR value of 'Meiju' was further verified as 677.5 CUs based on the UT model and morphological observation. As a kind of signal transducer, reactive oxygen species (ROS) released a signal to enter dormancy, which led to corresponding changes in carbohydrate and hormone metabolism in buds, thus promoting underground buds to acquire strong cold resistance and enter endodormancy. The expression of important genes related to ABA metabolism, such as NCED3, PP2C, CBF4 and ABF2, reached peaks at the critical stage of endodormancy release (9 January) and then decreased rapidly; the expression of the GA2ox8 gene related to GA synthesis increased significantly in the early stage of endodormancy release and decreased rapidly after the release of ecodormancy (23 January). Cytological observation showed that the period when the sugar and starch contents decreased and the ABA/GA ratio decreased was when 'Meiju' bud endodormancy was released. This study reveals the endodormancy regulation mechanism of 'Meiju' buds with the low-CR trait, which lays a theoretical foundation for breeding new herbaceous peony cultivars with the low-CR trait. [ABSTRACT FROM AUTHOR]

The compatibility of Bupleurum chinense DC (Chaihu)- Paeonia lactiflora Pall (Baishao) is one of the most accepted herb pairs in traditional Chinese medicine (TCM) prescriptions for treating depression. However, the combination mechanisms of this herb pair for anti-depression remain unclear. In this study, the combined effect of Chaihu-Baishao was evaluated by the chronic unpredictable mild stress (CUMS) rat model. Secondly, network pharmacology was constructed to dissect the united mechanisms. Based on the results of network pharmacology analysis, plasma metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was performed to discover the collaborative effect on metabolite regulation. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. The antidepressant effect of Chaihu-Baishao herb pair was significantly better than Chaihu or Baishao in sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). In network pharmacology, herb pair played synergetic effect through regulating shared pathways, such as MAPK signaling pathway and arachidonic acid metabolism, etc. Besides, by metabolomics, the herb pair improved more metabolites (14) than a single herb (10 & 9) and has a stronger regulation effect on metabolites. Correspondingly, herb pair adjusted more metabolism pathways (5) than individual herb (4 & 4). Furthermore, the arachidonic acid metabolism was selected as crucial metabolism pathways by a joint analysis of 199 targets and 14 metabolites. The results showed that herb pair regulated arachidonic acid metabolism by synergetic reducing the level of arachidonic acid, and inhibiting the enzyme activity of prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxide synthase 2 (PTGS2). This work provided an integrated strategy for revealing the combination mechanisms of Chaihu-Baishao herb pair for treating depression, and also a rational way for clarifying the composition rules of TCM. Image 1 • Dissected the combination mechanisms of Bupleurum chinense DC- Paeonia lactiflora Pall for treating depression. • Herb pair synergetically regulated shared pathways, and complementarily regulating unique pathways. • Herb pair improved more metabolites and adjusted more metabolism pathways than a single herb. • The arachidonic acid metabolism was selected as crucial metabolism pathways and experimentally validated by ELISA. [ABSTRACT FROM AUTHOR]

• Combination of macromonomer and metal ion pivot was used for reducing sites embedding of MIP. • OEG was used as macromonomer and Ni2+ was adopted as metallic pivot. • Necessity of simultaneous use of OEG macromonomer and Ni2+ was proved. • The Ni2+ OEG MIP made can be used for SPE to purify β -PGG from crude extract. 1,2,3,4,6-Penta-O-galloyl- β - d -glucose (β -PGG) is one of active component of polyphenol tannic acid in the rhizome of radix paeoniae alba , and isolating and purifying β -PGG from crude extract of Paeonia lactiflora Pall is rather challenge work. In this paper, to reduce the embedding of imprinted sites and increase the binding capacity, β -PGG imprinted monoliths were synthesized using a strategy of combination of hydrophilic macromonomer with metal ions as pivot. With a small side chain of oligoethylene glycol, oligo (ethyleneglycol) methyl ether methacrylate (OEG) was chosen as the hydrophilic macromonomer. 4-Vinylpyridine (4-VP) and ethyleneglycol dimethacrylate was used as functional monomer and crosslinker, respectively, and Ni2+ was adopted as metallic pivot. Polymerization parameters, including the ratio of functional monomer/template, ratios of 4-VP to Ni2+, and ratios of OEG to 4-VP on affinity of the resulting molecularly imprinted polymer (MIP) were systematically investigated. The structure and morphology of the obtained monolithic MIP was studied by field emission scanning electron microscopy and multipoint BET measurement. The greatest imprinting factor can be achieved to 68, which gave rise to excellent selectivity of the resulting MIP. When using the MIP as SPE absorbent, the mean recoveries for β -PGG were 74.1% with purity of 98.35%. The results demonstrated that the combination of metal ion pivot with hydrophilic macromonomer is effective approach to the balance of rigidity of imprinting cavities and polymer flexibility and increase the selectivity of the resulting MIP. [ABSTRACT FROM AUTHOR]

Background: Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway., Materials and Methods: Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico., Results: Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression., Conclusion: The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis.

Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. The root of Paeonia lactiflora Pall has been considered useful for the treatment of various disorders in traditional oriental medicine. Paeonol, found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, including anti-oxidative, anti-inflammatory and neuroprotective activities. The objective of this study was to examine the efficacy of paeonol in the repression of inflammation-induced neurotoxicity and microglial cell activation. Organotypic hippocampal slice cultures and primary microglial cells from rat brain were stimulated with bacterial lipopolysaccharide. Paeonol pretreatment was performed for 30 minutes prior to lipopolysaccharide addition. Cell viability and nitrite (the production of nitric oxide), tumor necrosis factor-alpha and interleukin-1beta products were measured after lipopolysaccharide treatment. In organotypic hippocampal slice cultures, paeonol blocked lipopolysaccharide-related hippocampal cell death and inhibited the release of nitrite and interleukin-1beta. Paeonol was effective in inhibiting nitric oxide release from primary microglial cells. It also reduced the lipopolysaccharide-stimulated release of tumor necrosis factor-alpha and interleukin-1β from microglial cells. Paeonol possesses neuroprotective activity in a model of inflammation-induced neurotoxicity and reduces the release of neurotoxic and proinflammatory factors in activated microglial cells.