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Widely targeted metabolomics of different tissues in Rubus corchorifolius

  • Xiangmei Chen EMAIL logo , Liang Liang , Shan Chang , Xiang Chun and Yun Qing
Published/Copyright: March 7, 2025

Abstract

Rubus corchorifolius, a medicinal plant of the Rosaceae family, is known for its diverse bioactive compounds. This study employs widely targeted metabolomics to investigate the metabolic profiles of leaf, stem, and flower tissue from R. corchorifolius. Using ultra-performance liquid chromatography coupled with tandem mass spectrometry, we identified 1,946 metabolites across the three tissue types. Multivariate statistical analyses revealed distinct metabolic signatures for each tissue, with flowers showing the most distinctive profile. Differential accumulation of flavonoids, phenolic acids, and primary metabolites reflected the specialised functions of each tissue type. Pathway enrichment analysis highlighted tissue-specific metabolic activities, including flavonoid biosynthesis in flowers and chlorophyll metabolism in leaves. This comprehensive metabolic characterisation provides a foundation for further investigations into the biosynthetic pathways and physiological functions of bioactive compounds in R. corchorifolius, potentially guiding future applications in medicine and agriculture.

1 Introduction

Natural products have long been recognised for their significant therapeutic potential in promoting human health. Recent studies have demonstrated the diverse applications of compounds derived from both plant and animal sources in preventing and treating various ailments. For instance, camel whey protein hydrolysates have shown promising effects in managing colorectal cancer by inducing G2/M cell cycle arrest [1]. Plant-based bioactive compounds, such as safranal from saffron, have exhibited hepatoprotective properties, offering potential strategies for addressing liver cancer through inhibition of oxidative stress and alleviation of inflammation [2]. Additionally, natural products have demonstrated efficacy in various health applications. Rhizoma polygonati compounds have shown potential in treating COVID-19, highlighting their possible role in antiviral therapy [3]. The combination of Hibiscus extract with cisplatin has demonstrated reduced liver toxicity while increasing effectiveness against lung cancer cells, suggesting a novel approach in cancer treatment [4]. Furthermore, the combination of crocin (a compound from saffron) with sorafenib has shown improved tumour-inhibiting effects in a rat model of cirrhotic hepatocellular carcinoma, indicating potential synergistic effects in cancer therapy [5].

Widely targeted metabolomics usually employs ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry and a pre-defined metabolite database for metabolite identification and quantification [6]. Compared with the traditional untargeted approach, widely targeted metabolomics greatly improves the efficiency and reliability of metabolite annotation. Meanwhile, it expands the metabolite coverage compared with targeted methods, which only focus on a limited number of known compounds [7]. Widely targeted metabolomics has been successfully applied to study the metabolic variations in various plant species and response to different biotic and abiotic factors [8,9,10].

Rubus corchorifolius, commonly known as library hook vine, is a perennial climbing shrub of the genus Rubus in the rose family (Rosaceae) [11]. It is native to East Asia and Southeast Asia, with a distribution spanning from Japan and Korea to China and Vietnam [12]. In China, R. corchorifolius is mainly found in the southern regions, including Zhejiang, Jiangxi, Fujian and Taiwan provinces [13]. R. corchorifolius is shrub with slender, prickly stems, simple ovate to lanceolate leaves, small white flowers, and aggregate red fruits. The fruits of R. corchorifolius, which turn red upon ripening, are edible and have a unique flavour. The leaves and roots of this plant are used as a folk medicine for treating various ailments, such as traumatic injury, rheumatoid arthritis and irregular menstruation [14]. Previous phytochemical studies have identified multiple bioactive constituents from R. corchorifolius, including triterpenes, flavonoids, tannins and steroids [15,16]. However, the overall metabolic profiles of different tissues in R. corchorifolius remain largely unexplored.

This study aims to address this knowledge gap by employing widely targeted metabolomics to investigate the tissue-specific metabolic profiles of R. corchorifolius. This work is essential because it will provide a comprehensive understanding of the metabolic composition across different plant tissues. The findings will have a significant impact on Rubus improvement by identifying metabolic markers associated with desirable traits. Moreover, these metabolomic studies will help enhance the content of desirable chemicals in this plant by elucidating biosynthetic pathways. While Rubus is not the sole natural source for any specific metabolite, it is known for its unique combination of bioactive compounds, particularly anthocyanins and ellagitannins. Our objectives are the following: (a) characterise the metabolic differences among leaf, stem and flower tissues; (b) identify key metabolites and pathways that contribute to the plant’s medicinal properties; and (c) provide a foundation for future studies on metabolic engineering and quality improvement in R. corchorifolius.

2 Materials and methods

2.1 Plant material and sample preparation

Rubus corchorifolius plants were collected from the natural habitats in Zhejiang Province, China, in May 2023. The mature leaves, stems and flowers were separately harvested, immediately frozen in liquid nitrogen and stored at −80°C until metabolite extraction.

For each tissue type, three biological replicates were prepared. The samples were ground into fine powder in liquid nitrogen using a mortar and pestle. Approximately 100 mg of powder was weighed and extracted with 1.2 ml pre-cooled 70% methanol (containing 0.1% formic acid) by vortexing for 30 s. The mixture was sonicated at 4°C for 10 min and then placed at −20°C for 1 h. After centrifugation at 12,000g and 4°C for 15 min, the supernatant was collected and filtered through a 0.22 μm membrane for liquid chromatography–mass spectrometry analysis.

Voucher specimens (XGZM230101, XGZM230102 and XGZM230103) have been deposited in the herbarium of Mongolian Medical College of Inner Mongolia Minzu University.

2.2 Widely targeted metabolomics

Metabolic profiling was performed on an ExionLC™ AD UPLC system coupled with a SCIEX Triple TOF 5600+ mass spectrometer (MS). Chromatographic separation was carried out on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm). The mobile phases consisted of (A) water containing 0.1% formic acid and (B) acetonitrile containing 0.1% formic acid. The elution gradient was set as follows: 0–1 min, 5% B; 1–9 min, 5–95% B; 9–10 min, 95% B; 10–10.1 min, 95–5% B; and 10.1–14 min, 5% B. The flow rate was 0.4 ml/min and the injection volume was 2 μl.

The MS was operated in both positive and negative ion modes. The electrospray ionisation source conditions were as follows: ion source gas 1, 60 psi; ion source gas 2, 60 psi; curtain gas, 30 psi; source temperature, 600°C; ion spray voltage floating, 5,500 V in positive mode and −4,500 V in the negative mode. The TOF MS scan range was 60–1,000 Da and the product ion scan range was 25–1,000 Da. The declustering potential and collision energy were optimised for individual metabolites.

2.3 Data processing and metabolite identification

The raw MS data were converted to mzXML files using the ProteoWizard MSConvert tool and processed with an in-house program, which was developed using R and based on XCMS for peak detection, extraction, alignment and integration. The metabolites were identified by matching the accurate mass-to-charge ratio values and MS/MS fragmentation patterns with a pre-constructed metabolite database, which contains information on >800 metabolite standards. The mass error threshold was set to 10 ppm and the MS/MS spectral similarity threshold was set to 0.8.

2.4 Statistical analysis

The processed metabolite data were normalised by the total peak intensity and subjected to log transformation and Pareto scaling before statistical analysis. The overall metabolic differences between tissue types were visualised using principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) in SIMCA software (version 14.1). The quality of the OPLS-DA model was assessed by the parameters R2X, R2Y, and Q2 and validated by a permutation test (n = 200).

The differential metabolites between tissue comparisons were determined by the combination of variable importance in projection (VIP) >1 from the OPLS-DA model and fold change (FC) >2 or <0.5. The hierarchical cluster analysis was performed using the “pheatmap” package in R to reveal the accumulation patterns of differential metabolites across samples.

Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted to explore the metabolic pathways that were significantly altered between tissues. The p-values were adjusted for multiple testing using the Benjamin–Hochberg method. Pathways with adjusted p-values of <0.05 were considered as significantly enriched.

3 Results

3.1 Overview of metabolite profiles in different tissues of R. corchorifolius

Using the widely targeted metabolomics approach, 1,946 metabolites were identified in the leaf, stem and flower tissues of R. corchorifolius. These metabolites belonged to diverse chemical classes, mainly including flavonoids, phenolic acids, amino acids and derivatives, lipids and organic acids (Figure 1a). The Venn diagram shows that 1,408 metabolites were commonly detected in all three tissues, while 363, 323 and 724 metabolites were uniquely identified in the leaf, stem and flower samples, respectively (Figure 1b).

Figure 1 
                  Metabolite profiling and analysis of different tissues in R. corchorifolius. (a) Distribution of main chemical classes among the detected metabolites. The pie chart illustrates the relative proportions of different metabolite classes, with flavonoids (26.31%) and phenolic acids (17.01%) being the most abundant. (b) Venn diagram showing the number of common and unique metabolites between RFl_vs_RFo (flower vs flower bud) and RFl_vs_RCa (flower vs calyx) comparisons; 724 metabolites are shared between the two comparisons. (c) PCA score plot of metabolite profiles in different tissues. Each point represents a sample, with colours indicating tissue types: RCa (green, calyx), RFo (orange, flower bud), RFl (purple, flower), and QC (pink, quality control). (d) OPLS-DA model validation by the permutation test. The graph shows the R2 and Q2 values for the original model (far right) and permuted models, indicating the model’s robustness and predictive power.
Figure 1

Metabolite profiling and analysis of different tissues in R. corchorifolius. (a) Distribution of main chemical classes among the detected metabolites. The pie chart illustrates the relative proportions of different metabolite classes, with flavonoids (26.31%) and phenolic acids (17.01%) being the most abundant. (b) Venn diagram showing the number of common and unique metabolites between RFl_vs_RFo (flower vs flower bud) and RFl_vs_RCa (flower vs calyx) comparisons; 724 metabolites are shared between the two comparisons. (c) PCA score plot of metabolite profiles in different tissues. Each point represents a sample, with colours indicating tissue types: RCa (green, calyx), RFo (orange, flower bud), RFl (purple, flower), and QC (pink, quality control). (d) OPLS-DA model validation by the permutation test. The graph shows the R2 and Q2 values for the original model (far right) and permuted models, indicating the model’s robustness and predictive power.

The PCA score plot reveals a clear separation between the three tissue types (Figure 1c). The first two principal components explained 64.8% of the total variance, with PC1 (45.3%) representing the difference between the flower and the other two tissues and PC2 (32%) representing the difference between the leaf and stem. The OPLS-DA model further demonstrated the distinctive metabolic phenotypes of different tissues (Figure 1d). The model parameters (R2X = 0.796, R2Y = 1, and Q2 = 0.992) indicated good fitness and predictability. No overfitting was observed in the permutation test.

3.2 Differential metabolites between tissues

To investigate the metabolic differences between tissues, pairwise comparisons were performed using the criteria of VIP >1 and FC >2 or <0.5. A total of 1,047, 1,087 and 947 metabolites were identified as differentially accumulated in flower vs stem, flower vs leaf and leaf vs stem comparisons, respectively. Interestingly, the number of upregulated metabolites was much higher than downregulated ones in both flower vs stem (790 vs 297) and flower vs leaf (773 vs 274) comparisons, implying the highly active metabolic status in flower tissue. In contrast, the leaf vs stem comparison showed a relatively balanced number of upregulated (493) and downregulated (454) metabolites.

The clustering heatmap displays the distinct accumulation patterns of differential metabolites across tissues (Figure 2). The flower samples were clearly separated from leaf and stem samples, and many metabolites showed higher abundance in flowers. The most abundant metabolites in flowers include several flavonoids, such as kaempferol and quercetin glycosides, which are important pigments for flower colouration and also possess antioxidant and ultraviolet (UV)-protective functions [17]. The leaf samples contained relatively higher levels of chlorophyll-related compounds, such as pheophorbide a and hydroxychlorophyll a, consistent with the primary role of leaves in photosynthesis. In addition, some phenolic acids (e.g. coumaric acid and caffeic acid derivatives) were enriched in leaves, which may be involved in defence against herbivores and pathogens [18]. The stem samples accumulated more organic acids and amino acids, including citric acid, malic acid and aspartic acid, which are important components for energy metabolism and nutrient transport [19].

Figure 2 
                  Hierarchical clustering heatmap of differential metabolites across tissues of R. corchorifolius. The heatmap displays the relative abundance of differential metabolites (rows) in different tissue samples (columns). The colour scale represents the Z-score normalised abundance, with red indicating high abundance and green indicating low abundance. Tissue types are labelled at the top: RCa (calyx), RFo (flower bud) and RFl (flower). The right-side bar shows the metabolite classes, revealing distinct accumulation patterns across tissues.
Figure 2

Hierarchical clustering heatmap of differential metabolites across tissues of R. corchorifolius. The heatmap displays the relative abundance of differential metabolites (rows) in different tissue samples (columns). The colour scale represents the Z-score normalised abundance, with red indicating high abundance and green indicating low abundance. Tissue types are labelled at the top: RCa (calyx), RFo (flower bud) and RFl (flower). The right-side bar shows the metabolite classes, revealing distinct accumulation patterns across tissues.

3.3 KEGG pathway analysis

To further understand the metabolic pathways involved in the tissue-specific accumulation of metabolites, KEGG enrichment analysis was performed. A total of 92, 89 and 93 pathways were significantly enriched (adjusted p < 0.05) for the differential metabolites in flower vs stem, flower vs leaf and leaf vs stem comparisons, respectively. The top enriched pathways are shown in Figure 3a.

Figure 3 
                  KEGG pathway enrichment analysis of differential metabolites between tissues of R. corchorifolius. (a) Bubble plot showing the top 20 enriched KEGG pathways. The x-axis represents the rich factor (ratio of differential metabolites to total metabolites in a pathway), and the y-axis lists the pathway names. Bubble size indicates the count of differential metabolites, while the colour represents the p-value (red: more significant, blue: less significant). (b) Heatmap of key differential metabolites involved in enriched pathways. Rows represent individual metabolites, and columns represent different tissue samples (RFl: flower, RCa: calyx). The colour scale indicates the relative abundance of metabolites (red: high, green: low).
Figure 3

KEGG pathway enrichment analysis of differential metabolites between tissues of R. corchorifolius. (a) Bubble plot showing the top 20 enriched KEGG pathways. The x-axis represents the rich factor (ratio of differential metabolites to total metabolites in a pathway), and the y-axis lists the pathway names. Bubble size indicates the count of differential metabolites, while the colour represents the p-value (red: more significant, blue: less significant). (b) Heatmap of key differential metabolites involved in enriched pathways. Rows represent individual metabolites, and columns represent different tissue samples (RFl: flower, RCa: calyx). The colour scale indicates the relative abundance of metabolites (red: high, green: low).

In the flower vs stem comparison, “flavonoid biosynthesis,” “flavone and flavonol biosynthesis” and “anthocyanin biosynthesis” were among the most significantly enriched pathways, which is in line with the abundant accumulation of flavonoids in flowers. The enrichment of the “phenylpropanoid biosynthesis” pathway was also observed, indicating the active biosynthesis of phenolic compounds. In addition, the “ABC transporters” pathway was highly enriched, suggesting the important roles of transporters in the distribution of metabolites between flowers and stems.

In the flower vs leaf comparison, besides the flavonoid-related pathways, “carotenoid biosynthesis” was significantly enriched. Carotenoids are a class of terpenoid pigments that contribute to the yellow, orange and red colours of the flowers [20]. The “cutin, suberin and wax biosynthesis” pathway was also enriched, consistent with the protective functions of cuticle and wax layers in aerial plant tissues.

For the leaf vs stem comparison, the most significantly enriched pathway was “porphyrin and chlorophyll metabolism,” reflecting the crucial roles of leaves in photosynthetic light harvesting. The enrichment of the “phenylpropanoid biosynthesis,” “flavonoid biosynthesis” and “stilbenoid, diarylheptanoid and gingerol biosynthesis” pathways indicated the accumulation of diverse phenolic compounds in leaves, which may be related to defence mechanisms. Moreover, several amino acid biosynthetic pathways, such as “phenylalanine, tyrosine and tryptophan biosynthesis” and “cysteine and methionine metabolism,” were also enriched, implying the active amino acid metabolism in leaves (Figure 3b).

4 Discussion

In this study, we applied a widely targeted metabolomics approach to investigate the metabolic profiles of different tissues (leaf, stem and flower) in R. corchorifolius. Our results revealed significant metabolic variations among tissues, with flowers exhibiting the most distinctive metabolite composition compared with leaves and stems.

The detection of 1,946 metabolites showcases the comprehensive coverage of widely targeted metabolomics in characterising plant metabolomes. Commonly identified metabolites provide a general metabolic background for R. corchorifolius, while tissue-specific metabolites indicate specialised functions of different organs.

Flavonoids accumulate abundantly in R. corchorifolius flowers, consistent with their role in flower colouration and pollinator attraction [21]. These compounds also protect reproductive tissues from oxidative damage and UV radiation [22]. The enrichment of flavonoid-related pathways in flowers supports their active biosynthesis.

Leaf tissues accumulated chlorophyll-related compounds and phenolic acids, essential for photosynthesis and defence mechanisms [23]. The stem tissue showed a high abundance of organic acids and amino acids, which are the key components in the central carbon and nitrogen metabolism [24]. This active primary metabolism in stems likely relates to their role in inter-organ connection and nutrient transport.

Our findings on the tissue-specific accumulation of metabolites in R. corchorifolius align with recent studies on metabolic profiling in other plant species. For instance, Nurtay et al. [25] demonstrated that metabolite distribution in different plant organs of Rhizoma polygonati from Mount Tai is closely related to their physiological functions and potential medicinal applications. The differential accumulation of bioactive compounds observed in our study is consistent with the findings of Nurtay et al. [25], who reported on the unique metabolic profile of Mount Tai-Rhizoma Polygonati and its potential applications in addressing chronic and hidden hunger, as well as its possible use as an anti-COVID-19 agent. This approach is further supported by Ahmad et al. [26] in their computational study on the androgen receptor as a potential anti-infective therapy target for COVID-19. Their study demonstrates the importance of understanding specific molecular interactions and motifs in natural compounds, which can be applied to the study of plant metabolites and their potential therapeutic applications. Additionally, the recent research by Ahmad et al. [27] on the microevolution and phylogenomic characterisation of respiratory syncytial virus highlights the significance of comprehensive mutational analysis across entire genomes. This approach could be adapted to plant metabolomics, providing more detailed insights into the genetic basis of metabolite production and accumulation in different plant tissues, thereby enhancing our understanding of the medicinal properties of plants such as R. corchorifolius.

It is worth noting that this study only focused on the metabolic profiles at one developmental stage of R. corchorifolius. The metabolite composition may exhibit dynamic changes during different growth and developmental stages, as well as under various environmental conditions [28]. Further studies are needed to investigate the temporal and spatial variations of metabolites in R. corchorifolius and to elucidate the underlying regulatory mechanisms.

Although this study provides a comprehensive metabolic profile of R. corchorifolius tissues, we recognise the need for further investigation into the biosynthetic pathways of the identified metabolites. Future studies should employ integrated omics approaches, combining metabolomics with transcriptomics and proteomics, to elucidate the enzymatic pathways and regulatory mechanisms underlying the production of key metabolites.

5 Conclusion

This study provides a comprehensive metabolic characterisation of leaf, stem and flower tissues in R. corchorifolius using widely targeted metabolomics. The distinct metabolite profiles and differentially accumulated metabolites among tissues reflect their specialised metabolic functions. The flavonoid-rich metabolite profile of flowers is associated with their ecological roles in attracting pollinators and protecting reproductive organs. The accumulation of chlorophyll-related compounds and phenolic acids in leaves is related to photosynthesis and defence responses. The stems are characterised by a relatively high abundance of primary metabolites involved in central metabolism. By identifying tissue-specific metabolite accumulation patterns, our study offers insights into the spatial regulation of secondary metabolism in this medicinal plant. This knowledge can guide future metabolic engineering efforts to enhance the production of desirable compounds, such as specific flavonoids or phenolic acids, in targeted tissues. Moreover, the identification of metabolic markers associated with different plant parts can contribute to the development of quality control measures for R. corchorifolius-derived products, ensuring consistency in their medicinal properties. Future studies building on these findings could focus on elucidating the regulatory mechanisms controlling the biosynthesis of key metabolites, potentially leading to strategies for optimising the nutritional and medicinal value of R. corchorifolius fruits and other plant parts.


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  1. Funding information: The study is funded by the Key Laboratory of Mongolian Medicine Research and Development Engineering Ministry of Education Open Project (MDK2023070).

  2. Author contributions: Chen XM conceived and designed the study. Liang L and Chang S collected the data. Chen XM, Chun X and Qing Y helped with the date analysis and statistics. All authors took part in drafting and revising the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

[1] Murali C, Mudgil P, Gan CY, Tarazi H, El-Awady R, Abdalla Y, et al. Camel whey protein hydrolysates induced G2/M cellcycle arrest in human colorectal carcinoma. Sci Rep. 2021;11(1):7062. 10.1038/s41598-021-86391-z.Search in Google Scholar PubMed PubMed Central

[2] Abdalla Y, Abdalla A, Hamza AA, Amin A. Safranal prevents liver cancer through inhibiting oxidative stress and alleviating inflammation. Front Pharmacol. 2022;12:777500. Published 2022 Feb 1. 10.3389/fphar.2021.777500.Search in Google Scholar PubMed PubMed Central

[3] Mu C, Sheng Y, Wang Q, Amin A, Li X, Xie Y. Dataset of potential Rhizoma Polygonati compound-druggable targets and partial pharmacokinetics for treatment of COVID-19. Data Brief. 2020;33:106475. Published 2020 Oct 30. 10.1016/j.dib.2020.106475.Search in Google Scholar PubMed PubMed Central

[4] Hamza AA, Heeba GH, Hassanin SO, Elwy HM, Bekhit AA, Amin A. Hibiscus-cisplatin combination treatment decreases liver toxicity in rats while increasing toxicity in lung cancer cells via oxidative stress- apoptosis pathway. Biomed Pharmacother. 2023;165:115148. 10.1016/j.biopha.2023.115148.Search in Google Scholar PubMed

[5] Awad B, Hamza AA, Al-Maktoum A, Al-Salam S, Amin A. Combining crocin and sorafenib improves their tumor-inhibiting effects in a rat model of diethylnitrosamine-induced cirrhotic-hepatocellular carcinoma. Cancers (Basel). 2023;15(16):4063. Published 2023 Aug 11. 10.3390/cancers15164063.Search in Google Scholar PubMed PubMed Central

[6] Wang XJ, Ren JL, Zhang AH, Sun H, Yan GL, Han Y, et al. Novel applications of mass spectrometry-based metabolomics in herbal medicines and its active ingredients: Current evidence. Mass Spectrom Rev. 2019;38(4–5):380–402. 10.1002/mas.21589.Search in Google Scholar PubMed

[7] Lyu R, Singh SK, Liu Y, Patra B, Zhou Y, Wang B, et al. Reprogramming plant specialized metabolism by manipulating protein kinases. Abiotech. 2021;2(3):226–39. 10.1007/s42994-021-00053-2.Search in Google Scholar PubMed PubMed Central

[8] Guo Q, Li X, Niu L, Jameson PE, Zhou W. Transcription-associated metabolomic adjustments in maize occur during combined drought and cold stress. Plant Physiol. 2021;186(1):677–95. 10.1093/plphys/kiab050.Search in Google Scholar PubMed PubMed Central

[9] Zhao X, Ji X, Mu Q, Feng S, Guo Y, Zhang C, et al. Comparative metabolomics of leaves and roots in response to cold stress in Poa pratensis. PLoS One. 2022;17(1):e0262345.Search in Google Scholar

[10] Zhang J, Wu X, Qiu J, Zhang L, Zhang Y, Qiu X, et al. Comprehensive comparison on the chemical profile of Guang Chen Pi at different ripeness stages using untargeted and pseudotargeted metabolomics. J Agric Food Chem. 2020;68(31):8483–95. 10.1021/acs.jafc.0c02904.Search in Google Scholar PubMed

[11] Yang Y, Zhang K, Xiao Y, Zhang L, Huang Y, Li X, et al. Genome assembly and population resequencing reveal the geographical divergence of Shanmei (Rubus corchorifolius). Genomics Proteom Bioinforma. 2022;20(6):1106–18. 10.1016/j.gpb.2022.05.003.Search in Google Scholar PubMed PubMed Central

[12] Kim JH, Kim W. Alleviation effects of Rubus coreanus Miquel root extract on skin symptoms and inflammation in chronic atopic dermatitis. Food Funct. 2022;13(5):2823–31. 10.1039/d1fo03580k.Search in Google Scholar PubMed

[13] Tian Y, Liimatainen J, Alanne AL, Lindstedt A, Liu P, Sinkkonen J, et al. Phenolic compounds extracted by acidic aqueous ethanol from berries and leaves of different berry plants. Food Chem. 2017;220:266–81. 10.1016/j.foodchem.2016.09.145.Search in Google Scholar PubMed

[14] Martini S, Conte A, Tagliazucchi D. Phenolic compounds profile and antioxidant properties of six sweet cherry (Prunus avium) cultivars. Food Res Int. 2017;97:15–26. 10.1016/j.foodres.2017.03.030.Search in Google Scholar PubMed

[15] Zhang Q, Tian G, Chen B, Cheng J. Triterpenes from Rubus corchorifolius. Nat Prod Res. 2013;27(21):2027–32.Search in Google Scholar

[16] Chen X, Gao Z, Song M, Ouyang W, Wu X, Chen Y, et al. Identification of terpenoids from Rubus corchorifolius L. f. leaves and their anti-proliferative effects on human cancer cells. Food Funct. 2017;8(3):1052–60. 10.1039/c6fo01343k.Search in Google Scholar PubMed

[17] Falcone Ferreyra ML, Rius SP, Casati P. Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front Plant Sci. 2012;3:222. 10.3389/fpls.2012.00222.Search in Google Scholar PubMed PubMed Central

[18] Sharma A, Shahzad B, Rehman A, Bhardwaj R, Landi M, Zheng B. Response of phenylpropanoid pathway and the role of polyphenols in plants under abiotic stress. Molecules. 2019;24(13):2452. 10.3390/molecules24132452.Search in Google Scholar PubMed PubMed Central

[19] Igamberdiev AU, Eprintsev AT. Organic acids: the pools of fixed carbon involved in redox regulation and energy balance in higher plants. Front Plant Sci. 2016;7:1042. 10.3389/fpls.2016.01042.Search in Google Scholar PubMed PubMed Central

[20] Sun T, Yuan H, Cao H, Yazdani M, Tadmor Y, Li L. Carotenoid metabolism in plants: the role of plastids. Mol Plant. 2018;11(1):58–74. 10.1016/j.molp.2017.09.010.Search in Google Scholar PubMed

[21] Shan X, Zhang Y, Peng W, Wang Z, Xie D. Molecular mechanism for jasmonate-induction of anthocyanin accumulation in Arabidopsis. J Exp Bot. 2009;60(13):3849–60. 10.1093/jxb/erp223.Search in Google Scholar PubMed

[22] Landi M, Tattini M, Gould KS. Multiple functional roles of anthocyanins in plant-environment interactions. Env Exp Bot. 2015;119:4–17. 10.1016/j.envexpbot.2015.05.012.Search in Google Scholar

[23] Heleno SA, Martins A, Queiroz MJ, Ferreira IC. Bioactivity of phenolic acids: metabolites versus parent compounds: a review. Food Chem. 2015;173:501–13. 10.1016/j.foodchem.2014.10.057.Search in Google Scholar PubMed

[24] Drincovich MF, Voll LM, Maurino VG. On the diversity of roles of organic acids. Front Plant Sci. 2016;7:1592. 10.3389/fpls.2016.01592.Search in Google Scholar PubMed PubMed Central

[25] Nurtay L, Sun Q, Mu C, Cao Z, Wang Q, Liang Z, et al. Rhizoma polygonati from Mount Tai: nutritional value and usefulness as a traditional Chinese medicine, source of herbzyme, and potential remediating agent for COVID-19 and chronic and hidden hunger. Acupunct Herb Med. 2021;1(1):31–8. 10.1097/HM9.0000000000000008.Search in Google Scholar PubMed PubMed Central

[26] Ahmad A, Makhmutova Z, Cao W, Majaz S, Amin A, Xie Y. Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach. Expert Rev Anti Infect Ther. 2023;21(3):317–27. 10.1080/14787210.2023.2179035.Search in Google Scholar PubMed

[27] Ahmad A, Majaz S, Saeed A, Noureen S, Rahman HU, Nouroz F, et al. Microevolution and Phylogenomic Characterization of Respiratory Syncytial Virus Type A: An Outlook of 2022-2023 Outbreak. Available at SSRN 4512922; 2024. 10.2139/ssrn.4410724.Search in Google Scholar

[28] Li J, Xiao Y, Zhou X, Liao Y, Wu S, Chen J, et al. Characterizing the cultivar-specific mechanisms underlying the accumulation of quality-related metabolites in specific Chinese tea (Camellia sinensis) germplasms to diversify tea products. Food Res Int. 2022;161:111824. 10.1016/j.foodres.2022.111824.Search in Google Scholar PubMed

Received: 2024-06-26
Revised: 2024-09-24
Accepted: 2024-10-07
Published Online: 2025-03-07

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  27. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  29. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  30. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  31. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  32. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  33. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  34. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
  38. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  40. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  41. A case of bloodstream infection caused by Neisseria gonorrhoeae
  42. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  43. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  44. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  45. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  46. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  47. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  48. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  49. Sodium butyrate aids brain injury repair in neonatal rats
  50. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  51. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  52. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  53. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  54. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  55. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  56. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  57. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  58. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  59. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  60. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  61. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  62. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  63. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  64. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  65. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  66. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  67. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  68. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  69. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  70. Oncolytic bacteria: A revolutionary approach to cancer therapy
  71. A de novo meningioma with rapid growth: A possible malignancy imposter?
  72. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  73. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  74. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  75. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  76. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  77. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  78. Evaluation and application analysis of animal models of PIPNP based on data mining
  79. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  80. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  81. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  82. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  83. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  84. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  85. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  86. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  87. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  88. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  89. RNF144A and RNF144B: Important molecules for health
  90. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  91. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  92. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  93. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  94. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  95. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  96. Understanding risk factors and prognosis in diabetic foot ulcers
  97. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  98. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  99. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  100. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  101. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  102. Pulmonary cryptococcosis with headache as the first presentation: A case report
  103. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  104. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  105. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  106. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  107. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  108. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  109. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  110. Wound healing and signaling pathways
  111. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  112. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  113. Ecology and Environmental Science
  114. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  115. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  116. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  117. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  118. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  119. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  120. Agriculture
  121. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  122. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  123. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  124. Animal Science
  125. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  126. Plant Sciences
  127. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  128. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  129. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  130. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  131. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  132. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  133. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  134. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  135. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  136. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  137. Food Science
  138. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  139. Review on role of honey in disease prevention and treatment through modulation of biological activities
  140. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  141. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  142. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  143. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  144. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  145. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  146. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  147. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  148. The dilemma of food genetics and improvement
  149. Bioengineering and Biotechnology
  150. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  151. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  152. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  153. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  154. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  155. Corrigendum
  156. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
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