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Keywords = Pseudostellaria heterophylla

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17 pages, 387 KiB  
Review
Chemical Properties, Preparation, and Pharmaceutical Effects of Cyclic Peptides from Pseudostellaria heterophylla
by Yue Yang, Luan Wen, Zhuang-Zhuang Jiang, Ben Chung-Lap Chan, Ping-Chung Leung, Chun-Kwok Wong and Ning-Hua Tan
Molecules 2025, 30(12), 2521; https://doi.org/10.3390/molecules30122521 - 9 Jun 2025
Viewed by 700
Abstract
Radix Pseudostellariae (Tai-Zi-Shen), the dried tuberous root of the Caryophyllaceae plant Pseudostellaria heterophylla (Miq.) Pax (P. heterophylla), has been widely used in traditional Chinese medicine (TCM) for thousands of years. It is slightly bitter, neutral in nature, associated with the spleen [...] Read more.
Radix Pseudostellariae (Tai-Zi-Shen), the dried tuberous root of the Caryophyllaceae plant Pseudostellaria heterophylla (Miq.) Pax (P. heterophylla), has been widely used in traditional Chinese medicine (TCM) for thousands of years. It is slightly bitter, neutral in nature, associated with the spleen and lung meridians, and used for nourishing qi, invigorating the spleen, as well as promoting body fluid production and moistening the lungs. In recent years, with the development in natural product chemistry, cyclic peptides, as some of the active constituents derived from P. heterophylla, have gained increasing attention. These cyclic peptides demonstrate a broad range of biological activities, including anticancer, antioxidant, and immunomodulatory effects, as well as cognitive benefits. This review provides an overview of the chemical characteristics and preparation strategies of cyclic peptides from P. heterophylla, and their biological activities and potential mechanisms are also described. The presented work establishes a scientific framework to facilitate the future research and development of P. heterophylla cyclic peptides as potential therapeutic agents. Full article
(This article belongs to the Special Issue Research Progress and Application of Natural Compounds—2nd Edition)
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18 pages, 8434 KiB  
Article
Long-Term Effects of Vegetative-Propagation-Mediated TuMV-ZR Transmission on Yield, Quality, and Stress Resistance in Pseudostellaria heterophylla
by Li Gu, Sheng Qian, Shuting Yao, Jiaxin Wu, Lianghong Wang, Jing Mu, Yankun Wang, Jianming Wang, Zhongyi Zhang and Mingjie Li
Pathogens 2025, 14(4), 353; https://doi.org/10.3390/pathogens14040353 - 5 Apr 2025
Viewed by 599
Abstract
Pseudostellaria heterophylla (Miq.) Pax (P. heterophylla) was a valued traditional Chinese herbal medicine. Previous studies have shown that P. heterophylla TuMV spreads during the vegetative propagation cycle using tuberous roots as carriers. However, the transmission mechanism of TuMV in P. heterophylla [...] Read more.
Pseudostellaria heterophylla (Miq.) Pax (P. heterophylla) was a valued traditional Chinese herbal medicine. Previous studies have shown that P. heterophylla TuMV spreads during the vegetative propagation cycle using tuberous roots as carriers. However, the transmission mechanism of TuMV in P. heterophylla and its effects on host growth remain to be elucidated. In this study, virus-free P. heterophylla culture seedlings were infected with control, TuMV-ZR, and TuMV-ZR-EGFP, thereby resulting in the initial infection cycle of IF1 (TIF1, TEIF1) and control NIF1, and used these roots to propagate the subsequent infection cycle IF2 (TIF2, TEIF2) and control NIF2. The transmission of TuMV-ZR seedlings was tracked by EGFP signal, and their yield, quality, and resistance were analyzed simultaneously in the critical growth period of the plants. The results indicated that TuMV-ZR accumulated in the tuberous roots of IF1 plants, subsequently migrated to IF2 during seedling growth, and was re-stored in IF2 tuberous roots, thereby forming a simple virus transmission cycle. Meanwhile, the tuberous roots of IF1 and IF2 P. heterophylla showed lower fresh weight, dry weight, soluble sugar, and saponin levels compared to NIF1 and NIF2, respectively. TuMV caused a significant reduction in chlorophyll synthesis in IF1 and IF2 P. heterophylla, resulting in impairment to their photosynthetic organs and efficiency. The measurement of stress resistance in IF1 and IF2 P. heterophylla revealed that continuous viral infection disrupted antioxidant enzyme activity, increased the content of MDA, enhanced the activity of PAL, and elevated the levels of intracellular osmotic substances in both propagation cycles. The findings indicated that the accumulation of the TuMV-ZR virus during two successive vegetative propagation cycles induced physiological stress, impaired photosynthesis, and caused progressive yield and quality decline with each cycle. This study systematically examined the impact of TuMV-ZR persistence during vegetative propagation on key physiological and biochemical indices in P. heterophylla, providing critical data to clarify vegetative-propagation-mediated germplasm degradation. Full article
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3 pages, 3551 KiB  
Correction
Correction: Li et al. Extraction of Polysaccharides from Root of Pseudostellaria heterophylla (Miq.) Pax. and the Effects of Ultrasound Treatment on Its Properties and Antioxidant and Immune Activities. Molecules 2024, 29, 142
by Hangyu Li, Ziwei Liu, Qianqian Liu, Xinnan Zhang, Sheng Li, Feng Tang, Linzi Zhang, Qian Yang, Qiran Wang, Shuyao Yang, Ling Huang, Yuwei Ba, Xihui Du, Falong Yang and Haibo Feng
Molecules 2025, 30(5), 1174; https://doi.org/10.3390/molecules30051174 - 6 Mar 2025
Viewed by 441
Abstract
Errors in Figure [...] Full article
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17 pages, 4623 KiB  
Article
Development of a TaqMan qPCR for the Simultaneous Detection of the TuMV and BBWV2 Viruses Responsible for the Viral Disease in Pseudostellaria heterophylla
by Li Gu, Chensi Liu, Shuting Yao, Jiaxin Wu, Lianghong Wang, Jing Mu, Yankun Wang, Jianming Wang, Zhongyi Zhang and Mingjie Li
Microorganisms 2024, 12(12), 2663; https://doi.org/10.3390/microorganisms12122663 - 22 Dec 2024
Cited by 1 | Viewed by 1014
Abstract
Pseudostellaria heterophylla (Miq.) Pax, a highly valued Chinese medicinal plant, is experiencing a notable decline in yield and quality due to viral diseases, particularly caused those by TuMV and BBWV2. Currently, the absence of a quantitative detection method for these viruses in P. [...] Read more.
Pseudostellaria heterophylla (Miq.) Pax, a highly valued Chinese medicinal plant, is experiencing a notable decline in yield and quality due to viral diseases, particularly caused those by TuMV and BBWV2. Currently, the absence of a quantitative detection method for these viruses in P. heterophylla impedes the accurate diagnosis. The development of an accurate quantitative detection method is thus essential for effectively managing viral diseases in this plant. In this study, singleplex and duplex TaqMan qPCR were developed for the detection of the two viruses, based on two viral cloning vectors. Concurrently, the levels of both viruses were examined in the main produced regions of P. heterophylla. Furthermore, the levels of BBWV2 were examined during its infection of P. heterophylla. The optimal singleplex qPCR employed 0.1 μM of hydrolysis probe and 0.1 μM of primer for TuMV, while 0.2 μM of hydrolysis probe and 0.1 μM of primer were utilised for BBWV2. In contrast, the duplex qPCR employed the use of 0.1 μM of the upstream/downstream primer from each primer pair, with 0.2 μM of the respective hydrolysis probes. The 95% limit of detection (LOD) for singleplex qPCR was 734 copies for TuMV and 20 copies for BBWV2, while the 95% LOD for duplex qPCR was 945 copies for TuMV and 47 copies for BBWV2. Furthermore, the intra- and inter-assay coefficients of variation were found to be less than 1.2% for both singleplex and duplex qPCR. Of the P. heterophylla sampled 60 sites, 96% were found to be infected by one of two viruses. The levels of BBWV2 in N. benthamiana and P. heterophylla demonstrated an initial increase, followed by a subsequent decrease. The TaqMan qPCR methods provide a technical foundation for the monitoring of virus infections in P. heterophylla. Full article
(This article belongs to the Section Virology)
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15 pages, 3322 KiB  
Article
Insights into the Genomic Background of Nine Common Chinese Medicinal Plants by Flow Cytometry and Genome Survey
by Chang An, Denglin Li, Lin Lu, Chaojia Liu, Xiaowen Xu, Shiyu Xie, Jing Wang, Ruoyu Liu, Chengzi Yang, Yuan Qin and Ping Zheng
Plants 2024, 13(24), 3536; https://doi.org/10.3390/plants13243536 - 18 Dec 2024
Viewed by 1561
Abstract
Medicinal plants have long played a crucial role in healthcare systems, but limited genomic information on these species has impeded the integration of modern biological technologies into medicinal plant research. In this study, we selected nine common medicinal plants, each belonging to a [...] Read more.
Medicinal plants have long played a crucial role in healthcare systems, but limited genomic information on these species has impeded the integration of modern biological technologies into medicinal plant research. In this study, we selected nine common medicinal plants, each belonging to a different plant family, including Sarcandra glabra (Chloranthaceae), Nekemias grossedentata (Vitaceae), Uraria crinita (Fabaceae), Gynostemma pentaphyllum (Cucurbitaceae), Reynoutria japonica (Polygonaceae), Pseudostellaria heterophylla (Caryophyllaceae), Morinda officinalis (Rubiaceae), Vitex rotundifolia (Lamiaceae), and Gynura formosana (Asteraceae), to estimate their genome sizes and conduct preliminary genomic surveys. The estimated genome sizes by flow cytometry were 3.66 Gb, 0.65 Gb, 0.58 Gb, 1.02 Gb, 3.96 Gb, 2.99 Gb, 0.43 Gb, 0.78 Gb, and 7.27 Gb, respectively. The genome sizes of M. officinalis, R. japonica, and G. pentaphyllum have been previously reported. Comparative analyses suggest that variations in genome size may arise due to differences in measurement methods and sample sources. Therefore, employing multiple approaches to assess genome size is necessary to provide more reliable information for further genomic research. Based on the genome survey, species with considerable genome size variation or polyploidy, such as G. pentaphyllum, should undergo a ploidy analysis in conjunction with population genomics studies to elucidate the development of the diversified genome size. Additionally, a genome survey of U. crinita, a medicinal plant with a relatively small genome size (509.08 Mb) and of considerable interest in southern China, revealed a low heterozygosity rate (0.382%) and moderate repeat content (51.24%). Given the limited research costs, this species represents a suitable candidate for further genomic studies on Leguminous medicinal plants characteristic of southern China. This foundational genomic information will serve as a critical reference for the sustainable development and utilization of these medicinal plants. Full article
(This article belongs to the Section Plant Molecular Biology)
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16 pages, 2521 KiB  
Article
Synergistic Effects of Oligochitosan and Pyraclostrobin in Controlling Leaf Spot Disease in Pseudostellaria heterophylla
by Cheng Zhang, Chenglin Tang, Qiuping Wang, Yue Su and Qinghai Zhang
Antibiotics 2024, 13(2), 128; https://doi.org/10.3390/antibiotics13020128 - 27 Jan 2024
Cited by 3 | Viewed by 1596
Abstract
Pseudostellaria heterophylla (or Taizishen in Chinese), a medicinal, edible, and ornamental Chinese herb, is seriously affected by leaf spot disease (LSD). Oligochitosan is a natural agricultural antibiotic that is produced via the degradation of chitosan, which is deacetylated from chitin; pyraclostrobin is a [...] Read more.
Pseudostellaria heterophylla (or Taizishen in Chinese), a medicinal, edible, and ornamental Chinese herb, is seriously affected by leaf spot disease (LSD). Oligochitosan is a natural agricultural antibiotic that is produced via the degradation of chitosan, which is deacetylated from chitin; pyraclostrobin is a broad-spectrum and efficient strobilurin fungicide. In this work, the ability of pyraclostrobin, oligochitosan, and their formula to manage P. heterophylla leaf spot disease and their role in its resistance, leaf photosynthesis, agronomic plant traits, root growth, and root quality were studied. The results show that the joint application of oligochitosan and low-dosage pyraclostrobin could control LSD more efficiently, with control effects of 85.75–87.49% compared to high-dosage pyraclostrobin or oligochitosan alone. Concurrently, the application of this formula could more effectively improve the resistance, leaf photosynthesis, agronomic plant traits, root yield, and medicinal quality of P. heterophylla, as well as reduce the application of pyraclostrobin. This finding suggests that 30% pyraclostrobin suspension concentrate (SC) 1500-time + 5% oligosaccharin aqueous solutions (AS) 500-time diluent can be recommended for use as a feasible formula to manage LSD and reduce the application of chemical pesticides. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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18 pages, 6341 KiB  
Article
Extraction of Polysaccharides from Root of Pseudostellaria heterophylla (Miq.) Pax. and the Effects of Ultrasound Treatment on Its Properties and Antioxidant and Immune Activities
by Hangyu Li, Ziwei Liu, Qianqian Liu, Xinnan Zhang, Sheng Li, Feng Tang, Linzi Zhang, Qian Yang, Qiran Wang, Shuyao Yang, Ling Huang, Yuwei Ba, Xihui Du, Falong Yang and Haibo Feng
Molecules 2024, 29(1), 142; https://doi.org/10.3390/molecules29010142 - 26 Dec 2023
Cited by 3 | Viewed by 1824 | Correction
Abstract
The hydrophilic polysaccharides (PS) were isolated and purified from the tuberous roots of Pseudostellaria heterophylla. The extraction process of PS from Pesudostellariae radix was optimized by single–factor experiments and orthogonal design. The extract was purified by DEAE cellulose column to obtain the [...] Read more.
The hydrophilic polysaccharides (PS) were isolated and purified from the tuberous roots of Pseudostellaria heterophylla. The extraction process of PS from Pesudostellariae radix was optimized by single–factor experiments and orthogonal design. The extract was purified by DEAE cellulose column to obtain the pure polysaccharide PHP. Then PHP was treated with different intensities of sonication to study the effect of sonication on PHP’s characteristics and its biological activity in vitro and in vivo. The results of this study revealed that ultrasound treatment did not significantly change the properties of PHP. Further, with the increase of ultrasound intensity, PHP enhanced the proliferation and phagocytosis of macrophage RAW264.7. Meanwhile, it could also significantly improve the body’s antioxidant activity and immune function. The results of this study demonstrated that PHP has the potential as a food additive with enhanced antioxidant and immune functions, and its biological activities could be enhanced by sonication. Full article
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19 pages, 3322 KiB  
Article
A Probiotic Bacillus amyloliquefaciens D-1 Strain Is Responsible for Zearalenone Detoxifying in Coix Semen
by Tao Deng, Yefei Chen, Jinqiang Zhang, Yanping Gao, Changgui Yang, Weike Jiang, Xiaohong Ou, Yanhong Wang, Lanping Guo, Tao Zhou and Qing-Song Yuan
Toxins 2023, 15(12), 674; https://doi.org/10.3390/toxins15120674 - 28 Nov 2023
Cited by 7 | Viewed by 2322
Abstract
Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp., which commonly and severely contaminate food/feed. ZEN severely affects food/feed safety and reduces economic losses owing to its carcinogenicity, genotoxicity, reproductive toxicity, endocrine effects, and immunotoxicity. To explore efficient methods to detoxify ZEN, we [...] Read more.
Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp., which commonly and severely contaminate food/feed. ZEN severely affects food/feed safety and reduces economic losses owing to its carcinogenicity, genotoxicity, reproductive toxicity, endocrine effects, and immunotoxicity. To explore efficient methods to detoxify ZEN, we identified and characterized an efficient ZEN-detoxifying microbiota from the culturable microbiome of Pseudostellaria heterophylla rhizosphere soil, designated Bacillus amyloliquefaciens D-1. Its highest ZEN degradation rate reached 96.13% under the optimal condition. And, D-1 can almost completely remove ZEN (90 μg·g−1) from coix semen in 24 h. Then, the D-1 strain can detoxify ZEN to ZEM, which is a new structural metabolite, through hydrolyzation and decarboxylation at the ester group in the lactone ring and amino acid esterification at C2 and C4 hydroxy. Notably, ZEM has reduced the impact on viability, and the damage of cell membrane and nucleus DNA and can significantly decrease the cell apoptosis in the HepG2 cell and TM4 cell. In addition, it was found that the D-1 strain has no adverse effect on the HepG2 and TM4 cells. Our findings can provide an efficient microbial resource and a reliable reference strategy for the biological detoxification of ZEN. Full article
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14 pages, 1227 KiB  
Article
Chitosan Enhances Low-Dosage Difenoconazole to Efficiently Control Leaf Spot Disease in Pseudostellaria heterophylla (Miq.) Pax
by Cheng Zhang, Yi Dai, Jiaqi Liu, Yue Su and Qinghai Zhang
Molecules 2023, 28(16), 6170; https://doi.org/10.3390/molecules28166170 - 21 Aug 2023
Cited by 3 | Viewed by 1894
Abstract
Pseudostellaria heterophylla (Miq.) Pax is a popular clinical herb and nutritious health food. However, leaf spot disease caused by fungal pathogens frequently occurs and seriously influences the growth, quality, and yield of P. heterophylla. In this work, the field control roles of [...] Read more.
Pseudostellaria heterophylla (Miq.) Pax is a popular clinical herb and nutritious health food. However, leaf spot disease caused by fungal pathogens frequently occurs and seriously influences the growth, quality, and yield of P. heterophylla. In this work, the field control roles of difenoconazole, chitosan, and their combination in the leaf spot disease in P. heterophylla and their effects on the disease resistance, photosynthetic capacity, medicinal quality, and root yield of P. heterophylla are investigated. The results manifest that 37% difenoconazole water-dispersible granule (WDG) with 5000-time + chitosan 500-time dilution liquid had a superior control capacity on leaf spot disease with the control effects of 91.17%~88.19% at 15~30 days after the last spraying, which significantly (p < 0.05) exceeded that of 37% difenoconazole WDG 3000-time dilution liquid and was significantly (p < 0.01) higher than that of 37% difenoconazole WDG 5000-time dilution liquid, chitosan 500-time dilution liquid, or chitosan 1000-time dilution liquid. Simultaneously, this combination could more effectively enhance the disease resistance, photosynthetic capacity, medicinal quality, and tuberous root yield of P. heterophylla compared to when these elements were applied alone, as well as effectively reduce difenoconazole application. This study emphasizes that chitosan combined with a low dosage of difenoconazole can be proposed as a green, efficient, and alternative formula for controlling leaf spot disease in P. heterophylla and enhancing its resistance, photosynthesis, quality, and yield. Full article
(This article belongs to the Special Issue Polysaccharide-Based Biopolymer: Recent Development and Applications)
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17 pages, 5735 KiB  
Article
Mitogen-Activated Protein Kinases SvPmk1 and SvMps1 Are Critical for Abiotic Stress Resistance, Development and Pathogenesis of Sclerotiophoma versabilis
by Felix Abah, Yunbo Kuang, Jules Biregeya, Yakubu Saddeeq Abubakar, Zuyun Ye and Zonghua Wang
J. Fungi 2023, 9(4), 455; https://doi.org/10.3390/jof9040455 - 7 Apr 2023
Cited by 6 | Viewed by 2256
Abstract
Mitogen-activated protein kinase (MAPK) signaling pathways are evolutionarily conserved in eukaryotes and modulate responses to both internal and external stimuli. Pmk1 and Mps MAPK pathways regulate stress tolerance, vegetative growth and cell wall integrity in Saccharomyces cerevisiae and Pyricularia oryzae. Here, we deployed [...] Read more.
Mitogen-activated protein kinase (MAPK) signaling pathways are evolutionarily conserved in eukaryotes and modulate responses to both internal and external stimuli. Pmk1 and Mps MAPK pathways regulate stress tolerance, vegetative growth and cell wall integrity in Saccharomyces cerevisiae and Pyricularia oryzae. Here, we deployed genetic and cell biology strategies to investigate the roles of the orthologs of Pmk1 and Mps1 in Sclerotiophoma versabilis (herein referred to as SvPmk1 and SvMps1, respectively). Our results showed that SvPmk1 and SvMps1 are involved in hyphal development, asexual reproduction and pathogenesis in S. versabilis. We found that ∆Svpmk1 and ∆Svmps1 mutants have significantly reduced vegetative growths on PDA supplemented with osmotic stress-inducing agents, compared to the wild type, with ∆Svpmps1 being hypersensitive to hydrogen peroxide. The two mutants failed to produce pycnidia and have reduced pathogenicity on Pseudostellaria heterophylla. Unlike SvPmk1, SvMps1 was found to be indispensable for the fungal cell wall integrity. Confocal microscopic analyses revealed that SvPmk1 and SvMps1 are ubiquitously expressed in the cytosol and nucleus. Taken together, we demonstrate here that SvPmk1 and SvMps1 play critical roles in the stress resistance, development and pathogenesis of S. versabilis. Full article
(This article belongs to the Special Issue Molecular Biology of Fungal Plant Pathogens)
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13 pages, 1505 KiB  
Article
The 5-Aminolevulinic Acid (5-ALA) Supplement Enhances PSII Photochemical Activity and Antioxidant Activity in the Late Growth Promotion of Pseudostellaria heterophylla
by Julin Ma, Meng Sun, Lingling Qiu, Yinfeng Xie, Yingli Ma and Wenchao Liang
Plants 2022, 11(22), 3035; https://doi.org/10.3390/plants11223035 - 10 Nov 2022
Cited by 11 | Viewed by 2369
Abstract
This study focused on the physiological regulation and mechanism of exogenous 5-aminolevulinic acid (5-ALA) in the late growth of P. heterophylla. In the middle of May, different concentrations of 5-ALA (0, 10, 20, 50 mg·L−1) were sprayed on the leaves. [...] Read more.
This study focused on the physiological regulation and mechanism of exogenous 5-aminolevulinic acid (5-ALA) in the late growth of P. heterophylla. In the middle of May, different concentrations of 5-ALA (0, 10, 20, 50 mg·L−1) were sprayed on the leaves. The effects of 5-ALA on tuberous root growth, antioxidant enzyme system, gas exchange, photosynthetic pigment contents and photosynthetic characteristics were measured from 23 May to 13 June. A concentration of 20 mg·L−1 of 5-ALA led to a significant increase in the yield of fresh root and biomass allocation at 38.12% and 25.07%, respectively, in comparation with the control (0 mg·L−1). The moderate concentration of 5-ALA statistically stimulated antioxidation activities. 5-ALA treatment enhanced photosynthetic activity and reduced photodamage. Compared to the control, there were increases in the chlorophyll fluorescence parameters of P. heterophylla under 5-ALA treatment. Moreover, 20 mg·L−1 of 5-ALA significantly changed the kinetic parameters of fluorescence. It enhanced the light absorption and distribution efficiency of PSII and the activities of leaves, resulting in alleviating photoinhibition by the excess excitation energy. The correlation indicated that there was a significant positive correlation between the yield of tuberous roots and biomass allocation, Pn and catalase (CAT), and a negative correlation between the yield of tuberous roots and malondialdehyde (MDA). The appropriate 5-ALA concentration in the late growth stage of P. heterophylla effectively enhanced the net photosynthetic capacity, mainly resulting from the enhancement of PSII photochemical activity to promote the increases in excitation energy absorption, capture and electron transfer efficiency of the leaves. Finally, 5-ALA treatment can increase the photochemical activity of PSII in the whole leaf and ultimately delay the senescence of P. heterophylla. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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26 pages, 16018 KiB  
Article
Investigating Potential GLP-1 Receptor Agonists in Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra, and Peptides Derived from Heterophyllin B for the Treatment of Type 2 Diabetes: An In Silico Study
by Hui-Jun Liao and Jason T. C. Tzen
Metabolites 2022, 12(6), 549; https://doi.org/10.3390/metabo12060549 - 15 Jun 2022
Cited by 11 | Viewed by 5368
Abstract
GLP-1 receptor agonists stimulate GLP-1R to promote insulin secretion, whereas DPP4 inhibitors slow GLP-1 degradation. Both approaches are incretin-based therapies for T2D. In addition to GLP-1 analogs, small nonpeptide GLP-1RAs such as LY3502970, TT-OAD2, and PF-06882961 have been considered as possible therapeutic alternatives. [...] Read more.
GLP-1 receptor agonists stimulate GLP-1R to promote insulin secretion, whereas DPP4 inhibitors slow GLP-1 degradation. Both approaches are incretin-based therapies for T2D. In addition to GLP-1 analogs, small nonpeptide GLP-1RAs such as LY3502970, TT-OAD2, and PF-06882961 have been considered as possible therapeutic alternatives. Pseudostellaria heterophylla, Linum usitatissimum, and Drymaria diandra are plants rich in cyclopeptides with hypoglycemic effects. Our previous study demonstrated the potential of their cyclopeptides for DPP4 inhibition. Reports of cyclic setmelanotide as an MC4R (GPCR) agonist and cyclic α-conotoxin chimeras as GLP-1RAs led to docking studies of these cyclopeptides with GLP-1R. Heterophyllin B, Pseudostellarin B, Cyclolinopeptide B, Cyclolinopeptide C, Drymarin A, and Diandrine C are abundant in these plants, with binding affinities of −9.5, −10.4, −10.3, −10.6, −11.2, and −11.9 kcal/mol, respectively. The configuration they demonstrated established multiple hydrogen bonds with the transmembrane region of GLP-1R. DdC:(cyclo)-GGPYWP showed the most promising docking score. The results suggest that, in addition to DPP4, GLP-1R may be a hypoglycemic target of these cyclopeptides. This may bring about more discussion of plant cyclopeptides as GLP-1RAs. Moreover, peptides derived from the HB precursor (IFGGLPPP), including IFGGWPPP, IFPGWPPP, IFGGYWPPP, and IFGYGWPPPP, exhibited diverse interactions with GLP-1R and displayed backbones available for further research. Full article
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18 pages, 6894 KiB  
Article
Physicochemical Characteristics and Antidiabetic Properties of the Polysaccharides from Pseudostellaria heterophylla
by Yingying Liu, Yongjun Kan, Yating Huang, Chang Jiang, Li Zhao, Juan Hu and Wensheng Pang
Molecules 2022, 27(12), 3719; https://doi.org/10.3390/molecules27123719 - 9 Jun 2022
Cited by 18 | Viewed by 2958
Abstract
This study aimed to investigate the Pseudostellaria heterophylla polysaccharides (PF40) physicochemical and antidiabetic characteristics. The ultraviolet–visible (UV) spectra, Fourier transform infrared radiation (FT-IR) spectra, nuclear magnetic resonance (NMR) spectra, zeta potential, surface characteristics, and conformational and thermal stability properties of PF40 were characterized. [...] Read more.
This study aimed to investigate the Pseudostellaria heterophylla polysaccharides (PF40) physicochemical and antidiabetic characteristics. The ultraviolet–visible (UV) spectra, Fourier transform infrared radiation (FT-IR) spectra, nuclear magnetic resonance (NMR) spectra, zeta potential, surface characteristics, and conformational and thermal stability properties of PF40 were characterized. X-ray diffraction (XRD) and scanning electron microscopy (SEM), combined with Congo red test, revealed that PF40 powder has mainly existed in amorphous form with triple-helix conformation. The single-molecular structure of PF40 exhibited a multi-branched structure extending from the center to the periphery by scanning probe microscopy (SPM) scanning. The monosaccharide residue of PF40 was an α-pyranoid ring and exhibits good stability below 168 °C. Experimental studies on antidiabetic characteristics found that PF40 could significantly improve STZ-induced intestinal mucosal damage and reduce the apoptosis of villus epithelial cells. PF40 combined with metformin could significantly improve the symptoms of insulin resistance in type 2 diabetes mellitus (T2DM) rats, the molecular mechanism might be through inhibiting the expression of RORγ protein and increasing Foxp3 protein in the jejunum of T2DM rats, and then restoring the STZ-induced imbalance of T helper 17(Th17)/ regulatory T cells (Treg) cells, thereby maintaining intestinal immune homeostasis. Results identified in this study provided important information regarding the structure and antidiabetic characteristics of Pseudostellaria heterophylla polysaccharides, which can contribute to the development of Pseudostellaria heterophylla polysaccharides for industrial purposes in the future. Full article
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13 pages, 1342 KiB  
Article
Use of Fluorescent 2-AB to Explore the Bidirectional Transport Mechanism of Pseudostellaria heterophylla Polysaccharides across Caco-2 Cells
by Bin Yang, Yuan Li, Wentao Shi, Yingying Liu, Yongjun Kan, Jinlong Chen, Juan Hu and Wensheng Pang
Molecules 2022, 27(10), 3192; https://doi.org/10.3390/molecules27103192 - 17 May 2022
Cited by 9 | Viewed by 2634
Abstract
Polysaccharides are abundant in natural resources and perform numerous physiological functions. Polysaccharide structures often lack chromophore groups; thus, current analytical methods cannot distinguish polysaccharide metabolites in the body or polysaccharide prototypes in biological samples. Thus, the measurement of polysaccharides in blood, bodily fluid, [...] Read more.
Polysaccharides are abundant in natural resources and perform numerous physiological functions. Polysaccharide structures often lack chromophore groups; thus, current analytical methods cannot distinguish polysaccharide metabolites in the body or polysaccharide prototypes in biological samples. Thus, the measurement of polysaccharides in blood, bodily fluid, and cell-culture medium is difficult. Our early-stage research resulted in the isolation of two homogeneous polysaccharides from Pseudostellaria heterophylla, PHP0.5MSC-F and PHPH-1-2, which have anti-hyperglycemia and insulin resistance improvement effects for type 2 diabetes. In this study, the reducing terminal sugars of PHP0.5MSC-F and PHPH-1-2 were labeled with 2-aminobenzamide (2-AB) to prepare novel fluorescent probes for HPLC-coupled fluorescence detection (HPLC-FLD). Quantitative analysis was performed in reference to T40, and the detection limit for PHP0.5MSC-F was found to be 8.84 μg/mL with a linear range of 29.45–683.28 μg/mL. In reference to T70, the detection limit for PHPH-1-2 was found to be 13.89 μg/mL with a linear range of 46.29–462.76 μg/mL. This method was used to measure the bidirectional transport of polysaccharides across caco-2 cells from apical to basolateral (AP→BL) or from basolateral to apical (BL→AP) directions and to evaluate the polysaccharide bioavailability. The drug absorption capacity was determined based on the apparent permeability coefficient (Papp), and the Papp values for the two polysaccharides were found to be greater than 1 × 10−6 cm/s, which suggests easy absorption. Regarding bidirectional transport, the AP→BL Papp values were greater than the BL→AP values; thus, PHP0.5MSC-F and PHPH-1-2 mainly underwent passive transference. The two membrane permeable polysaccharides were not P-gp efflux transporter substrates. The absorption mechanism of PHP0.5MSC-F complies with passive diffusion under a concentration gradient, whereas PHPH-1-2 mainly utilizes a clathrin-mediated endocytic pathway to enter caco-2 cells. This innovative HPLC-FLD method can help to track polysaccharide internalization in vitro and in vivo to facilitate cellular uptake and biodistribution exploration. Full article
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25 pages, 17836 KiB  
Article
The Potential Role of Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum and Drymaria diandra, and Peptides Derived from Heterophyllin B as Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: An In Silico Study
by Hui-Jun Liao and Jason T. C. Tzen
Metabolites 2022, 12(5), 387; https://doi.org/10.3390/metabo12050387 - 24 Apr 2022
Cited by 7 | Viewed by 4483
Abstract
Dipeptidyl peptidase 4 (DPP4) inhibitors can treat type 2 diabetes by slowing GLP-1 degradation to increase insulin secretion. Studies have reported that Pseudostellaria heterophylla, Linum usita-tissimum (flaxseed), and Drymaria diandra, plants rich in Caryophyllaceae-type cyclopeptides and commonly used as herbal or [...] Read more.
Dipeptidyl peptidase 4 (DPP4) inhibitors can treat type 2 diabetes by slowing GLP-1 degradation to increase insulin secretion. Studies have reported that Pseudostellaria heterophylla, Linum usita-tissimum (flaxseed), and Drymaria diandra, plants rich in Caryophyllaceae-type cyclopeptides and commonly used as herbal or dietary supplements, are effective in controlling blood sugar. The active site of DPP4 is in a cavity large enough to accommodate their cyclopeptides. Molecular modeling by AutoDock Vina reveals that certain cyclopeptides in these plants have the potential for DPP4 inhibition. In particular, “Heterophyllin B” from P. heterophylla, “Cyclolinopeptide C” from flaxseed, and “Diandrine C” from D. diandra, with binding affinities of −10.4, −10.0, and −10.7 kcal/mol, are promising. Docking suggests that DPP4 inhibition may be one of the reasons why these three plants are beneficial for lowering blood sugar. Because many protein hydrolysates have shown the effect of DPP4 inhibition, a series of peptides derived from Heterophyllin B precursor “IFGGLPPP” were included in the study. It was observed that IFWPPP (−10.5 kcal/mol), IFGGWPPP (−11.4 kcal/mol), and IFGWPPP (−12.0 kcal/mol) showed good binding affinity and interaction for DPP4. Various IFGGLPPP derivatives have the potential to serve as scaffolds for the design of novel DPP4 inhibitors. Full article
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