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-1β), 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.

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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

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.

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.

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.

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.

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.

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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

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%.

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.
OBJECTIVE: 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.
CONCLUSIONS: JROL could be used as a potential new source for treating UC.