The phytochemistry and pharmacology of three Rheum species: A comprehensive review with future perspectives.

BACKGROUND: Rheum palmatum, R. tanguticum, and R. officinale, integral species of the genus Rheum, are widely used across global temperate and subtropical regions. These species are incorporated in functional foods, medicines, and cosmetics, recognized for their substantial bioactive components. PURPOSE: This review aims to synthesize developments from 2014 to 2023 concerning the botanical characteristics, ethnopharmacology, nutritional values, chemical compositions, pharmacological activities, mechanisms of action, and toxicity of these species. METHODS: Data on the three Rheum species were gathered from a comprehensive review of peer-reviewed articles, patents, and clinical trials accessed through PubMed, Google Scholar, Web of Science, and CNKI. RESULTS: The aerial parts are nutritionally rich, providing essential amino acids, fatty acids, and minerals, suitable for use as health foods or supplements. Studies have identified 143 chemical compounds, including anthraquinones, anthrones, flavonoids, and chromones, which contribute to their broad pharmacological properties such as laxative, anti-diarrheal, neuroprotective, hepatoprotective, cardiovascular, antidiabetic, antitumor, anti-inflammatory, antiviral, and antibacterial effects. Notably, the materials science approach has enhanced understanding of their medicinal capabilities through the evaluation of bioactive compounds in different therapeutic contexts. CONCLUSION: As medicinal and economically significant herb species, Rheum species provide both edible aerial parts and medicinal underground components that offer substantial health benefits. These characteristics present new opportunities for developing nutritional ingredients and therapeutic products, bolstering the food and pharmaceutical industries.

Scorch processing of rhubarb (Rheum tanguticum Maxim. ex Balf.) pyrolyzed anthraquinone glucosides into aglycones and improved the therapeutic effects on thromboinflammation via regulating the complement and coagulation cascades pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. AIM OF THE STUDY: This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. MATERIALS AND METHODS: The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. RESULTS: Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. CONCLUSIONS: Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.

Antiepileptic and Neuroprotective Effects of Rheum tanguticum Root Extract on Trimethyltin-Induced Epilepsy and Neurodegeneration: In Vivo and in Silico Analyses.

BACKGROUND: Rheum tanguticum root, cataloged as "Daehwang" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5). CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.

[Pseudo-targeted metabolomics for differential components of Rhei Radix et Rhizoma from three plant species].

Rhei Radix et Rhizoma is common traditional Chinese medicine with multiple original plants. The content and proportion of the active components in Rhei Radix et Rhizoma from different plant species were compared to accurately evaluate the medicine qua-lity and provide a theoretical basis for precise use of this medicine in clinical practice. In this study, fresh Rhei Radix et Rhizoma samples were collected from the four-year-old plants of Rheum palmatum, R. tanguticum, and R. officinale. The relative content of 220 anthraquinones, anthrones, and tannins in the samples were determined by pseudo-targeted metabolomics, and the differential components were screened by multivariate statistical methods. The principal component analysis classified the samples into three clusters according to the original plants. The orthogonal partial least squares-discriminant analysis(OPLS-DA) screened out 117 differential components, including 8 free anthraquinones, 18 anthraquinone glycosides, 80 anthrones, and 11 tannins. Twenty-eight components had the highest content in R. tanguticum, mainly including sennosides, anthraquinone glycosides, and procyanidins. Thirty-five components showed the highest content in R. officinale, mainly including free anthraquinones and catechines. Fifty-four components showed the highest content in R. palmatum, mainly including dianthrones, while the structures of most of them cannot be determined temporarily. The content distribution of differential components in the three original plants indicates that R. tanguticum has the strongest effect of purging, while R. officinale has the strongest effect of clearing heat and purging fire, and both have stronger effects of resolvong stasis and dredging meridians than R. palmatum.

[UPLC-QE-Orbitrap-MS combined with network pharmacology to explore differential components and mechanisms of raw and scorched rhubarb for treatment of ulcerative colitis].

This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC) and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS) and network pharmacology. The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model. The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents, while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels. UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb. Multivariate statistical methods were used to screen components increasing significantly after the scorching process. The seven compounds included five free anthraquinones, gallic acid, and 5-hydroxymethylfurfural(HMF). Meanwhile, the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds. Network pharmacology and molecular docking suggested that free anthraquinones, gallic acid, and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2), epidermal growth factor receptor(EGFR), tumor necrosis factor(TNF), and caspase-3(CASP3) and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt), hypoxia inducible factor-1(HIF-1), TNF, and mitogen-activated protein kinase(MAPK), so as to regulate the inflammation response, oxidative stress, and cell apoptosis to relieve UC symptoms. This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb, providing the clinical reference for using rhubarb to treat UC.

[Effect and mechanism of free total rhubarb anthraquinones on pyroptosis of J774A.1 macrophages].

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.

Fe(III)/peroxymonosulfate oxidation system for the degradation of rhein, a toxic component abundance in rhubarb residue.

Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage ecology and even hazard human health if left untreated. In this study, the degradation effects of bisulfite- (BS) and peroxymonosulfate- (PMS) based oxidation systems on rhein in rhubarb residue were compared and investigated. The effects of BS and PMS with two valence states of ferric ion (Fe) on the degradation of rhein in rhubarb residue were optimized for the selection of optimal oxidation system. The influences of reaction temperature, reaction time and initial pH on the removal of rhein under the optimal oxidation system were evaluated. The chemical profiles of rhubarb residue with and without oxidation process were compared by UPLC-QTOF-MS/MS, and the degradation effects were investigated by PLS-DA and S plot/OPLS-DA analysis. The results manifested that PMS showed relative higher efficiency than BS on the degradation of rhein. Moreover, Fe(III) promoted the degradation effect of PMS, demonstrated that Fe(III)/PMS is the optimal oxidation system to degrade rhein in rhubarb residue. Further studies indicated that the degradation of rhein by the Fe(III)/PMS oxidation system was accelerated with the prolong of reaction time and the elevation of reaction temperature, and also affected by the initial pH. More importantly, Fe(III)/PMS oxidation system could degrade rhein in rhubarb residue completely under the optimal conditions. In conclusion, Fe(III)/PMS oxidation system is a feasible method to treat rhein in rhubarb residue.

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

Magnetic-stirring-enhanced mechanical amorphous dispersion extraction for the hydrophobic phytochemical constituents using an aqueous solution from a medicinal plant.

A method involving chitosan-assisted magnetic-stirring-enhanced mechanical amorphous dispersion extraction was developed and utilized to extract hydrophobic anthraquinones from Rhei Radix et Rhizoma prior to ultrahigh performance liquid chromatography analysis. Incorporating natural chitosan as a dispersant facilitated the extraction of hydrophobic anthraquinones using purified water, considerably enhancing the eco-friendliness of the extraction methodology. To optimize extraction efficiency, an extensive evaluation of the crucial parameters influencing rhubarb yield was conducted. Furthermore, a response surface methodology was applied to optimize the extraction conditions. Under these optimized conditions, the method exhibited linearity ranges of 0.1-100 µg/mL, with correlation coefficients between 0.9990 and 0.9998. The method's intraday (n = 6) and interday (n = 6) precision levels were maintained at ≤3.58%, which was considered to be within acceptable limits. The computed detection and quantification limits were 16.54-24.60 and 54.91-82.04 ng/mL, respectively. Consequently, this optimized method was effectively employed to extract five specific compounds (aloe-emodin, emodin, rhein, chrysophanol, and physcion) from Rhei Radix et Rhizoma, achieving recoveries ranging from 86.43% to 102.75%.

Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment.

BACKGROUND: Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE: To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS: The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS: Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION: RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.

Mid-infrared spectroscopic identification of the right-baked rhubarb for ulcerative colitis therapy.

Clinical and experimental evidences have confirmed the significant therapeutic effects of rhubarb on ulcerative colitis (UC), but the strong purgative function of rhubarb also aggravates UC symptoms such as bloody diarrhea. Stir-baking to scorch is a traditional Chinese medicinal processing method that can eliminate the adverse purgative function while keep or even enhance the UC therapeutic function of rhubarb. However, the under-baked rhubarb still have the undesirable purgative function, but the over-baked rhubarb may lose the required medicinal functions. Therefore, the determination of the right endpoint is the primary quality concern about the baking process of rhubarb. In this research, typical anthraquinone compounds and mid-infrared (MIR) spectra were recruited to determine the best baking degree of rhubarb for UC therapy. Raw rhubarb slices were baked at 180 °C with rotation to prepare the rhubarbs with different baking degrees. The right-baked rhubarb was defined according to the UC therapeutic responses as well as the traditional color criterion. Referring to the typical anthraquinone compounds in rhubarb slices and extracts, the baking degree of rhubarb may be assessed by the conversion ratio of anthraquinone glycosides to anthraquinone aglycones. MIR spectra showed the gradual decompositions of organic compounds including anthraquinone glycosides and tannins during the baking process. Rhubarbs with different baking degrees can be distinguished clearly by MIR-based principal component analysis. In conclusion, the ratio of anthraquinone glycosides to anthraquinone aglycones may be a reasonable chemical indicator of the right-baked rhubarb. Meanwhile, MIR spectroscopy can identify the right-baked rhubarb simply and rapidly.

A chromosome-level genome reveals genome evolution and molecular basis of anthraquinone biosynthesis in Rheum palmatum.

BACKGROUND: Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. RESULTS: We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. CONCLUSION: Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.

Optimized therapeutic potential of Yinchenhao decoction for cholestatic hepatitis by combined network meta-analysis and network pharmacology.

BACKGROUND: Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD. PURPOSE: To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored. METHODS: We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques. RESULTS: Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness. CONCLUSION: Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.

The chemical composition, protective effect of Rheum officinale leaf juice and its mechanism against dextran sulfate sodium-induced ulcerative colitis.

BACKGROUND: Rhubarb is widely distributed and cultivated worldwide, and its leaves presented antioxidant activity and could be used as food additive. However, the chemical ingredients, and protective effect of Rheum officinale leaf juice (JROL) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) are still unclear. PURPOSE: This paper sought to the characterization and functional properties of JROL, and explore the underlying mechanism on UC mice. METHODS: UPLC-ESI-Q-TOF/MS and other analytical instruments were employed to determine the chemical ingredients of JROL. After inducing UC model using 3% DSS, multiple biological methods were used to evaluate its protective effect and the potential mechanism. RESULTS: JROL is rich in proximate compositions and minerals and has high nutritional value, and contains reducing sugars, polysaccharides and pectin. Fifteen compounds were identified using UPLC-ESI-Q-TOF/MS. Among them, rutin has the highest content (2.22 %) in UPLC analysis. JROL presented protective effect on DSS-induced UC, and alleviated morphological alterations and ultra-structural feature of tissue, and the polysaccharides and flavonoids may contribute to its protective effect. JROL inhibited NF-κB/NLRP3 signaling pathway to alleviate inflammatory response, oxidative stress and intestinal injury by decreasing the expression of p-p65, p-IκBα, NLRP3, ASC, etc.. Moreover, it up-regulated the expression of tight junction proteins, and re-balanced the disturbance of gut microbiota to regulate the inflammatory response. Finally, a correlation among the inflammatory response, NF-κB/NLRP3 pathway and gut microbiota was established. Moreover, JROL presented the safety in the acute toxicity test. CONCLUSION: JROL could be used as a potential new source for treating UC.

Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis.

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

Rhubarb powder: Potential uses as a functional bread ingredient.

As a traditional staple food, bread lacks several nutrients such as fiber and minerals. In this study, the possibilities of using rhubarb powder to enrich wheat bread were investigated. Rhubarb powder was replaced with wheat flour at the ratios of 0%, 4%, 8%, and 12%. In order to reveal effects of rhubarb powder on quality properties of bread, color, moisture, total protein, fat content, antioxidant activity, textural, and sensory analysis were conducted. As the rhubarb powder ratio increased, the fiber (10.60 ± 0.55), ash (4.34 ± 0.13), and fat content (2.17 ± 0.55) of bread samples increased significantly (p < 0.05). Antioxidant activity (19.61% ± 0.53%) and total phenolic contents (916.38 ± 2.69) of bread samples also increased significantly (p < 0.05). The colors of the enriched breads were relatively dark. The breads containing 12% rhubarb powder had the highest ash content (4.34 ± 0.13). The samples containing 4% rhubarb powder took the highest sensory scores from the sensory panel in terms of odor, flavor, and overall impression. However, as the ratio of rhubarb powder increased, the sensory values of bread samples decreased. According to the results of this study, rhubarb powder could be used up to 4% to produce acceptable breads in terms of sensory properties with improved nutritional quality.

Prediction of potential mechanisms of rhubarb therapy for colorectal cancer based on network pharmacological analysis and molecular docking.

The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.

Metabolomics analysis reveals the metabolite profiles of Rheum tanguticum grown under different altitudinal gradients.

BACKGROUND: Plant growth and quality are often affected by environmental factors, including geographical location, climate, and soil. In this study, we describe the effect of altitudinal differences on the growth and active ingredients in Rheum tanguticum Maxim. ex Balf. (R. tanguticum), a traditional Chinese medicinal herb known for its laxative properties. RESULTS: The results showed that plants grown at lower altitudes had better growth performances than those in higher altitude areas. The yield varied by 2.45-23.68 times with altitude, reaching a maximum of 102.01 t/ha. In addition, total anthraquinone and total sennoside contents decreased with increasing altitude, whereas total tannins increased with increasing altitude. The total anthraquinone content of the indicator compound reached 5.15% at five experimental sites, which exceeded the Chinese Pharmacopoeia standard by 70.87%. The content of the other two categories of active ingredients reached a maximum value of 0.94% (total sennosides) and 2.65% (total tannins). Redundancy analysis revealed that annual rainfall, annual average temperature, annual sunshine hours, and pH significantly affected growth and active ingredients. Moreover, key metabolites, such as flavonoids, amino acids and their derivatives, phenolic acids, lipids, and terpenes, were differentially expressed between samples from low- and high-altitude cultivation areas. These metabolites were enriched in the flavonoid and flavonol biosynthetic pathway and the monoterpene biosynthetic pathway. CONCLUSIONS: These results suggest that high anthraquinone content was observed in the lowest-latitude cultivation area due to low rainfall and alkaline soil pH. Key metabolites were significantly upregulated in high-latitude cultivation areas. These results provide a scientific basis for quality control and the systematic cultivation of R. tanguticum.

Rheum khorasanicum. Hydroalcoholic root extract induces cell death in human colorectal adenocarcinoma: An in vitro and in silico study.

Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay's finding indicated that 100, 60, and 30µg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells.