Recent trends in treatment strategies for Alzheimer's disease and the challenges: A topical advancement.

Alzheimer's Disease (AD) is an irreversible and progressive neurological disease that has affected at least 50 million people around the globe. Considering the severity of the disease and the continuous increase in the number of patients, the development of new effective drugs or intervention strategies for AD has become urgent. AD is caused by a combination of genetic, environmental, and lifestyle factors, but its exact cause has not yet been clarified. Given the current challenges being faced in the clinical treatment of AD, such as complex AD pathological network and insufficient early diagnosis, herein, we have focused on the three core pathological features of AD, including amyloid-ß (Aß) aggregation, tau phosphorylation and tangles, and activation of inflammatory factors. In this review, we have briefly underscored the primary evidence supporting each pathology and discuss AD pathological network among Aß, tau, and inflammation. We have also comprehensively summarized the most instructive drugs and their treatment strategies against Aß, tau, or neuroinflammation used in basic research and clinical trials. Finally, we have discussed and outlined the pros and cons of each pathological approach and looked forward to potential personalized diagnosis and treatment strategies that are beneficial to AD patients.

Integrative lipidomics profile uncovers the mechanisms underlying high-level α-linolenic acid accumulation in Paeonia rockii seeds.

Tree peony (Paeonia rockii) is an excellent woody oilseed crop, known for its high α-linolenic acid (ALA, ~45%) content, which is of great value for human health. However, the mechanisms underlying this high-level ALA accumulation in tree peony seeds are poorly understood. In this study, we evaluated the dynamic changes in the lipidomic profile of P. rockii seeds during development. A total of 760 lipid molecules were identified in P. rockii seeds; triacylglycerol (TAG) lipid molecules showed the highest abundance and diversity, both increasing during seed development. Particularly, ALA was the predominant fatty acid at the TAG sn-3 position. We further characterized two diacylglycerol acyltransferase (DGAT) genes and three phospholipid:diacylglycerol acyltransferase (PDAT) genes involved in the transfer of fatty acids to the TAG sn-3 position. Gene expression and subcellular localization analyses suggested that PrDGATs and PrPDATs may function as endoplasmic reticulum-localized proteins in seed TAG biosynthesis. In vitro functional complementation analysis showed different substrate specificities, with PrPDAT2 having a specific preference for ALA. Multiple biological assays demonstrated that PrDGAT1, PrDGAT2, PrPDAT1-2, and PrPDAT2 promote oil synthesis. Specifically, PrPDAT2 leads to preferential ALA in the oil. Our findings provide novel functional evidence of the roles of PrDGAT1 and PrPDAT2, which are potential targets for increasing the ALA yield in tree peony and other oilseed crops.

Secondary Metabolomic Analysis and In Vitro Bioactivity Evaluation of Stems Provide a Comprehensive Comparison between Dendrobium chrysotoxum and Dendrobium thyrsiflorum.

The stems of Dendrobium chrysotoxum (DC) are commonly used as health-promoting foods due to their excellent biological activities. However, the stems of D. thyrsiflorum (DT) are often used to meet the scarcity of DC in production because of their highly similar morphology. However, the related metabolomic and bioactive information on the stems of DC and DT are largely deficient. Here, secondary metabolites of DC and DT stems were identified using an ultra-performance liquid chromatography-electrospray ionization-mass spectrometry, and their health-promoting functions were evaluated using several in vitro arrays. A total of 490 metabolites were identified in two stems, and 274 were significantly different. We screened out 10 key metabolites to discriminate the two species, and 36 metabolites were determined as health-promoting constituents. In summary, DT stems with higher extract yield, higher total phenolics and flavonoids, and stronger in vitro antioxidant activities demonstrated considerable potential in food and health fields.

Tree peony transcription factor PrWRI1 enhances seed oil accumulation.

BACKGROUND: WRINKLED1 (WRI1) encodes a transcription factor, belonging to the APETALA2 (AP2) family, and plays a key role in regulating plant oil biosynthesis. As a newly woody oil crop, tree peony (Paeonia rockii) was notable for the abundant unsaturated fatty acids in its seed oil. However, the role of WRI1 during the accumulation of P. rockii seeds oil remains largely unknown. RESULTS: In this study, a new member of the WRI1 family was isolated from P. rockii and was named PrWRI1. The ORF of PrWRI1 consisted of 1269 nucleotides, encoding a putative protein of 422 amino acids, and was highly expressed in immature seeds. Subcellular localization analysis in onion inner epidermal cells showed that PrWRI1 was located at the nucleolus. Ectopic overexpression of PrWRI1 could significantly increase the total fatty acid content in Nicotiana benthamiana leaf tissue and even PUFAs in transgenic Arabidopsis thaliana seeds. Furthermore, the transcript levels of most genes related to fatty acids (FA) synthesis and triacylglycerol (TAG) assembly were also up-regulated in transgenic Arabidopsis seeds. CONCLUSIONS: Together, PrWRI1 could push carbon flow to FA biosynthesis and further enhance the TAG amount in seeds with a high proportion of PUFAs.

Corrigendum: A Tree Peony Trihelix Transcription Factor PrASIL1 Represses Seed Oil Accumulation.

[This corrects the article DOI: 10.3389/fpls.2021.796181.].

A Tree Peony Trihelix Transcription Factor PrASIL1 Represses Seed Oil Accumulation.

In many higher plants, seed oil accumulation is governed by complex multilevel regulatory networks including transcriptional regulation, which primarily affects fatty acid biosynthesis. Tree peony (Paeonia rockii), a perennial deciduous shrub endemic to China is notable for its seed oil that is abundant in unsaturated fatty acids. We discovered that a tree peony trihelix transcription factor, PrASIL1, localized in the nucleus, is expressed predominantly in developing seeds during maturation. Ectopic overexpression of PrASIL1 in Nicotiana benthamiana leaf tissue and Arabidopsis thaliana seeds significantly reduced total fatty acids and altered the fatty acid composition. These changes were in turn associated with the decreased expression of multitudinous genes involved in plastidial fatty acid synthesis and oil accumulation. Thus, we inferred that PrASIL1 is a critical transcription factor that represses oil accumulation by down-regulating numerous key genes during seed oil biosynthesis. In contrary, up-regulation of oil biosynthesis genes and a significant increase in total lipids and several major fatty acids were observed in PrASIL1-silenced tree peony leaves. Together, these results provide insights into the role of trihelix transcription factor PrASIL1 in controlling seed oil accumulation. PrASIL1 can be targeted potentially for oil enhancement in tree peony and other crops through gene manipulation.

Phytochemical components and bioactivities of novel medicinal food - Peony roots.

Peony as an important medicinal material is widely cultivated in China, which is one of the natural distribution centers of wild peony species. So far, however, there has not been a systematic study of the roots from China's wild peonies. In this study, the total phenolic (TPC), total flavonoid (TFC), other secondary metabolites, and microelement content, as well as the antioxidant, antibacterial, anticholinesterase, and antitumor activities of peony roots from 15 species and 2 subspecies were measured. Thirteen secondary metabolites were detected, with Paeoniflorin and Paeonol being the highest content bio-activities compounds. Additionally, the peony roots had a significant antioxidant activities and bacteriostatic effect against Gram-positive bacteria, with MIC varying from 0.063 to 1 mg/mL. P. anomala subsp. veitchii and P. lactiflora showed outstanding anticholinesterase capacities and cytotoxic activities. Taken together, the data presented here provide new insights into both the medicinal and edible potential of roots from wild peony species.

New Insights into the Impact of Ecological Factor on Bioactivities and Phytochemical Composition of Paeonia veitchii.

Paeonia veitchii has been widely distributed in China under different ecological types. Its roots contain diverse phytochemical constituents, which possess very high bioactivities. However, the influence of ecological factors on activities and ingredients of P. veitchii roots still remains unknown. The purpose of this research was to analyze the variation in bioactivities and phytochemical composition of P. veitchii roots upon exposure to various ecological factors. Seven P. veitchii populations collected from different regions in China were evaluated. The results of correlation analysis suggested that four major ecological factors, including average annual temperature, elevation, total potassium, and organic matter, had a strong correlation with the bioactivities of P. veitchii roots. Further, the major ecological factors were also highly correlated with the contents of naringin, gallic acid, benzoylpaeoniflorin, and paeoniflorin. The principal component analysis results supported four major metabolites as the main contributing ingredients. All populations were classified into three groups, G1, G2, and G3, through hierarchical cluster analysis. G1 showed more significant advantages in the above-mentioned four ecological factors, four active ingredients, and bioactivities compared to the other two groups. P. veitchii roots growing at lower average annual temperature, high elevation, rich total potassium and organic matter in the soils were presumed to have relatively higher bioactivities. These data expand the study on the bioactivities and phytochemical composition of P. veitchii roots and have a guiding significance for the ecological factor selection during the cultivation process of this herbaceous peony species.

Insights into the Phytochemical Composition and Bioactivities of Seeds from Wild Peony Species.

Peony is an important medicinal and ornamental plant widely cultivated in the world. Its seeds as a functional food source have attracted much more attention in recent years, and they are rich in monoterpene glycosides and phenolic compounds. To assess the application value of wild peony seeds, the main chemical composition and content, such as total phenolic content (TPC), total flavonoid content (TFC), total flavanol content (TAC), and α and γ tocopherol content, of the seeds from 12 species and 2 subspecies were systematically explored in the present study. Four different antioxidant assays (DPPH, ABTS, FRAP, and HRSA), antibacterial, and antifungal assays were also performed using various in vitro biochemical methods. The results showed that the seeds of P. delavayi, P. obovata. subsp. obovata, and P. rockii. subsp. rockii had a high content of TPC, TFC, and TAC, respectively. Twenty-five individual chemical compounds were qualitatively and quantitatively measured by HPLC-MS, with paeoniflorin being the most abundant compound in all samples. P. mairei was grouped individually into a group via hierarchical cluster analysis according to its relatively highest monoterpene glycosides and TPC content. This work has provided a basis for the development and utilization of seeds for the selection of wild peony species of dietary interest.

Virus-induced gene silencing in the perennial woody Paeonia ostii.

Tree peony is a perennial deciduous shrub with great ornamental and medicinal value. A limitation of its current functional genomic research is the lack of effective molecular genetic tools. Here, the first application of a Tobacco rattle virus (TRV)-based virus-induced gene silencing (VIGS) in the tree peony species Paeonia ostii is presented. Two different approaches, leaf syringe-infiltration and seedling vacuum-infiltration, were utilized for Agrobacterium-mediated inoculation. The vacuum-infiltration was shown to result in a more complete Agrobacterium penetration than syringe-infiltration, and thereby determined as an appropriate inoculation method. The silencing of reporter gene PoPDS encoding phytoene desaturase was achieved in TRV-PoPDS-infected triennial tree peony plantlets, with a typical photobleaching phenotype shown in uppermost newly-sprouted leaves. The endogenous PoPDS transcripts were remarkably down-regulated in VIGS photobleached leaves. Moreover, the green fluorescent protein (GFP) fluorescence was detected in leaves and roots of plants inoculated with TRV-GFP, suggesting the capability of TRV to silence genes in various tissues. Taken together, the data demonstrated that the TRV-based VIGS technique could be adapted for high-throughput functional characterization of genes in tree peony.

Phenotypic Characteristics and Fatty Acid Composition of Seeds from Different Herbaceous Peony Species Native to China.

Herbaceous peony has been widely cultivated in China due to its substantial ornamental and medicinal value. In the present study, the phenotypic characteristics, total fatty acid (FA) content, and nine FA compositions of herbaceous peony seeds from 14 populations belonging to six species and one subspecies were determined by normal test and gas chromatography/mass spectrometry (GC/MS). The results showed that the phenotypic characteristics of seeds varied dramatically among species. The concentrations of five major FAs in seed oils were as follows: linoleic acid (173.95-236.51 µg/mg), linolenic acid (227.82-302.71 µg/mg), oleic acid (135.32-208.81 µg/mg), stearic acid (6.52-11.7 µg/mg), and palmitic acid (30.67-47.64 µg/mg). Correlation analysis demonstrated that oleic acid had the highest partial correlation coefficient with total FAs and might be applied to develop a model of phenotypic characteristics. FAs were significantly influenced by the following environmental factors: latitude, elevation, and annual average temperature. Based on the FA levels in the seed oils, clustering analysis divided 14 populations into two clusters. It was found that the average contents of oleic acid, linoleic acid, and total FAs in cluster I (147.16 µg/mg, 200.31 µg/mg, and 671.24 µg/mg, respectively) were significantly lower than those in cluster II (196.65 µg/mg, 220.16 µg/mg, and 741.78 µg/mg, respectively). Cluster I was perfectly consistent with subsect. Foliolatae, while cluster II was in good agreement with subsect. Dissectifoliae. Therefore, the FA composition of wild herbaceous peony seed oil might be used as a chemotaxonomic marker.

Comparative Transcriptome Analysis Reveals an Efficient Mechanism of α-Linolenic Acid in Tree Peony Seeds.

Tree peony (Paeonia section Moutan DC.) species are woody oil crops with high unsaturated fatty acid content, including α-linolenic acid (ALA/18:3; >40% of the total fatty acid). Comparative transcriptome analyses were carried out to uncover the underlying mechanisms responsible for high and low ALA content in the developing seeds of P. rockii and P. lutea, respectively. Expression analysis of acyl lipid metabolism genes revealed upregulation of select genes involved in plastidial fatty acid synthesis, acyl editing, desaturation, and triacylglycerol assembly in seeds of P. rockii relative to P. lutea. Also, in association with ALA content in seeds, transcript levels for fatty acid desaturases (SAD, FAD2, and FAD3), which encode enzymes necessary for polyunsaturated fatty acid synthesis, were higher in P. rockii compared to P. lutea. Furthermore, the overexpression of PrFAD2 and PrFAD3 in Arabidopsis increased linoleic and ALA content, respectively, and modulated the final ratio 18:2/18:3 in the seed oil. In conclusion, we identified the key steps and validated the necessary desaturases that contribute to efficient ALA synthesis in a woody oil crop. Together, these results will aid to increase essential fatty acid content in seeds of tree peonies and other crops of agronomic interest.

Fatty Acid and Associated Gene Expression Analyses of Three Tree Peony Species Reveal Key Genes for α-Linolenic Acid Synthesis in Seeds.

The increasing demand for healthy edible oil has generated the need to identify promising oil crops. Tree peony (Paeonia section Moutan DC.) is a woody oil crop with α-linolenic acid (ALA) contributing for 45% of the total fatty acid (FA) content in seeds. Molecular and genetic differences that contribute to varied FA content and composition among the wild peony species are, however, poorly understood. Analyses of FA content and composition during seed development in three tree peony species (Paeonia rockii, P. potaninii, and P. lutea) showed varied FA content among them with highest in P. rockii, followed by P. potaninii, and P. lutea. Total FA content among these species increased with seed development and reached its maximum in its final stage. Seed FA composition analysis of the three species also revealed that ALA (C18:3) was the most abundant, followed by oleic (C18:1) and linoleic (C18:2) acids. Additionally, quantitative real-time RT-PCR analyses of 10 key seed oil synthesis genes in the three tree peony species revealed that FAD3, FAD2, ß-PDHC, LPAAT, and Oleosin gene expression levels positively correlate with total FA content and rate of accumulation. Specifically, the abundance of FAD3 transcripts in P. rockii compared with P. potaninii, and P. lutea suggests that FAD3 might play an important role in synthesis of ALA via phosphatidylcholine-derived pathway. Overall, comparative analyses of FA content and composition in three different peony species revealed a correlation between efficient lipid accumulation and lipid gene expression during seed development. Further characterization and metabolic engineering of these key genes from peonies will allow for subsequent improvement of tree peony oil quality and production.