BACKGROUND: Rheum palmatum (RP) is a widely used traditional herb, which possesses antioxidant properties, inhibits ROS production and reduces fever.
OBJECTIVE: The aim of this study was to examine the antioxidative properties of the water extract of RP on oxidative-stressed mice.
METHODS: Forty mice were administered with DL-homocysteine (DL-Hcy) to induce oxidative stress and were divided into four groups: 1) CK: NaCl and water; 2) DL-Hcy: DL-Hcy and water; 3) DL-Hcy+50RP: DL-Hcy with 50 mg kg-1 body weight (BW) d-1 RP; and 4) DL-Hcy+150RP: DL-Hcy with 150 mg kg-1 BW d-1 RP. Rhein (0.3 mg g-1 dry matter) was the main active ingredient in RP.
RESULTS: When compared with Dl-Hcy mice, the mice with supplementary RP mitigated oxidative stress by reducing the liver concentrations of superoxide dismutase (SOD) by 27% and glutathione peroxidase (GSH-Px) by 32%, and the reactive oxygen species (ROS) in the kidney and spleen. These responses were more pronounced in DL-Hcy+150RP than DL-Hcy+50RP mice. RP also exhibited therapeutic effects on liver steatosis, chronic kidney nephritis and intestinal villus width shortening caused by oxidative stress, and concomitantly decreased the serum glucose concentration (RP vs. DL-HCY, 2.3 vs. 4.1 mmol L-1).
CONCLUSIONS: It was concluded that RP possesses antioxidant and therapeutic properties that can mitigate lesions on organs and prevent diabetes in oxidative-stressed mice. This study highlights the potential of RP as a medicinal supplement for animals in the future.

BACKGROUND: Rheum palmatum L. has important medicinal value because it contains biologically active anthraquinones. However, the key genes and TFs involved in anthraquinone biosynthesis and regulation in R. palmatum remain unclear.
METHODS: Based on full length transcriptome data, in this study, we screened the differentially expressed genes in the anthraquinone biosynthesis pathway. The R2R3-MYB family genes of R. palmatum were systematically identified based on full-length transcriptome sequencing followed by bioinformatics analyses. The correlation analysis was carried out by using co-expression analysis, protein interaction analysis, and real-time fluorescence quantitative analysis after MeJA treatment. The RpMYB81 and RpMYB98 genes were amplified by RT-PCR, and their subcellular localization and self-activation characteristics were analyzed.
RESULTS: Comparative transcriptome analysis results revealed a total of 3525 upregulated and 6043 downregulated DEGs in the CK versus MeJA group; 28 DEGs were involved in the anthraquinone pathway. Eleven CHS genes that belonged to the PKS family were differentially expressed and involved in anthraquinone biosynthesis. Twelve differentially expressed MYBs genes were found to be co-expressed and interact with CHS genes. Furthermore, 52 MYB genes were identified as positive regulators of anthraquinone biosynthesis and were further characterized. Three MYB genes including RpMYB81, RpMYB98, and RpMYB100 responded to MeJA treatment in R. palmatum, and the levels of these genes were verified by qRT-PCR. RpMYB81 was related to anthraquinone biosynthesis. RpMYB98 had an interaction with genes in the anthraquinone biosynthesis pathway. RpMYB81 and RpMYB98 were mainly localized in the nucleus. RpMYB81 had self-activation activity, while RpMYB98 had no self-activation activity.
CONCLUSIONS: RpMYB81, RpMYB98, and RpMYB100 were significantly induced by MeJA treatment. RpMYB81 and RpMYB98 are located in the nucleus, and RpMYB81 has transcriptional activity, suggesting that it might be involved in the transcriptional regulation of anthraquinone biosynthesis in R. palmatum.

BACKGROUND: Pancreatic lipase is one of the most important key targets in the treatment of obesity. Inhibition of pancreatic lipase can effectively reduce lipid absorption and treat obesity and other related metabolic disorders.
OBJECTIVE: The goal of this study is the efficient screening of pancreatic lipase inhibitors in the root and rhizome of Rheum palmatum using affinity ultrafiltration-high-performance liquid chromatography (AUF-HPLC) combined with high-resolution inhibition profiling (HRIP).
METHODS: Potential pancreatic lipase ligands and pancreatic lipase inhibitors in ethyl acetate fraction of R. palmatum were screened using AUF-HPLC and HRIP, respectively. All screened compounds were identified by HPLC- quadrupole time-of-flight (Q-TOF)/MS. Eight compounds were screened out by both AUF-HPLC and HRIP, and six compounds were screened out by either AUF-HPLC or HRIP alone. The pancreatic lipase inhibitory activities of all screened compounds were verified by enzyme inhibition assay and molecular docking.
RESULTS: Five new potent pancreatic lipase inhibitors were discovered, namely procyanidin B5 3,3\'-di-O-gallate (IC50 = 0.06 ± 0.01 μM), 1,6-di-O-galloyl-2-O-cinnamoyl-β-D-glucoside (IC50 = 12.83 ± 0.67 μM), 1-O-(1,3,5-trihydroxy)phenyl-2-O-galloyl-6-O-cinnamoyl-β-D-glucoside (IC50 = 17.84 ± 1.33 μM), 1,2-di-O-galloyl-6-O-cinnamoyl-β-D-glucoside (IC50 = 18.39 ± 1.52 μM), and 4-(4\'-hydroxyphenyl)-2-butanone-4\'-O-β-D-(2\"-O-galloyl-6\"-O-cinnamoyl)-glucoside (IC50 = 2.91 ± 0.40 μM). It was found that procyanidin B5 3,3\'-di-O-gallate showed higher pancreatic lipase inhibitory activity than the positive control orlistat (IC50 = 0.12 ± 0.02 μM).
CONCLUSIONS: The combination of affinity ultrafiltration-high-performance liquid chromatography (AUF-HPLC) and high-resolution inhibition profiling (HRIP) could reduce the risk of false-negative screening and missed screening and could achieve more efficient screening of bioactive compounds in complex natural products.

Parkinson\'s disease (PD) is one of the large-scale health issues detrimental to human quality of life, and current treatments are only focused on neuroprotection and easing symptoms. This study evaluated in silico binding activity and estimated the stability of major metabolites in the roots of R. palmatum (RP) with main protein targets in Parkinson\'s disease and their ADMET properties. The major metabolites of RP were subjected to molecular docking and QSAR with α-synuclein, monoamine oxidase isoform B, catechol o-methyltransferase, and A2A adenosine receptor. From this, emodin had the greatest binding activity with Parkinson\'s disease targets. The chemical stability of the selected compounds was estimated using density functional theory analyses. The docked compounds showed good stability for inhibitory action compared to dopamine and levodopa. According to their structure-activity relationship, aloe-emodin, chrysophanol, emodin, and rhein exhibited good inhibitory activity to specific targets. Finally, mediocre pharmacokinetic properties were observed due to unexceptional blood-brain barrier penetration and safety profile. It was revealed that the major metabolites of RP may have good neuroprotective activity as an additional hit for PD drug development. Also, an association between redox-mediating and activities with PD-relevant protein targets was observed, potentially opening discussion on electrochemical mechanisms with biological functions.

Tyrosinase (TYR) plays a key role in the enzymatic reaction that is responsible for a range of unwanted discoloration effects, such as food browning and skin hyperpigmentation. TYR inhibitors could, therefore, be candidates for skin care products that aim to repair pigmentation problems. In this study, we used a metabolomics approach combined with the isobologram analysis to identify anti-TYR compounds within natural resources, and evaluate their possible synergism with each other. Rheum palmatum was determined to be a model plant for observing the effect, of which seven extracts with diverse phytochemicals were prepared by way of pressurized solvent extraction. Each Rheum palmatum extract (RPE) was profiled using nuclear magnetic resonance spectroscopy and its activity of tyrosinase inhibition was evaluated. According to the orthogonal partial least square analysis used to correlate phytochemicals in RPE with the corresponding activity, the goodness of fit of the model (R2 = 0.838) and its predictive ability (Q2 = 0.711) were high. Gallic acid and catechin were identified as the active compounds most relevant to the anti-TYR effect of RPE. Subsequently, the activity of gallic acid and catechin were evaluated individually, and when combined in various ratios by using isobologram analysis. The results showed that gallic acid and catechin in the molar ratios of 9:5 and 9:1 exhibited a synergistic inhibition on TYR, with a combination index lower than 0.77, suggesting that certain combinations of these compounds may prove effective for use in cosmetic, pharmaceutical, and food industries.

Rheum palmatum, a well-known Traditional Chinese Medicines (TCM), has been used for medical purposes for thousand years in China. However, endophyte diversity of R. palmatum among different tissues and ages is still not revealed. In this study, we used 16S and ITS amplicon sequencing and combined with PICRUSt and FUNGuild to compare endophyte diversity and ecological function among different tissues and ages of R. palmatum. The results showed that the diversity and OTUs (Operational taxonomic units) abundance of endophytic fungi and bacteria of R. palmatum differed among different tissues and ages. The predictive function analysis showed that metabolism was main function of endophytic bacteria in different tissue and year samples, while saprotroph was dominant trophic mode of endophytic fungi in different year samples. The dominant trophic modes of endophytic fungi were saprotroph, pathotroph-symbiotroph and symbiotroph, and relative abundances differed in the different tissue samples. Our results elucidated the comprehensive diversity and composition profiles of endophytes in different tissues and year of R. palmatum. Our data offered pivotal information to clarify the role of endophytes in the production of R. palmatum and its important metabolites.

Trichoderma spp. are an important plant-growth-promoting fungi. Trichoderma citrinoviride HT-1 was isolated from Rheum palmatum root, which has beneficial effects on growth and metabolite accumulation. However, the improvement mechanisms for growth and metabolite accumulation of T. citrinoviride HT-1 are unclear. In this study, RNA sequencing (RNA-seq) and high-performance liquid chromatography (HPLC) were used to measure the effect of different concentrations of conidial suspension of the HT-1 strain on the growth promotion and metabolite accumulation of R. palmatum seedlings. The results showed that the highest biomass and metabolites of R. palmatum seedlings were obtained through treatment with the HT-1 strain at a final spore concentration of 107 spores/mL. RNA sequencing indicated that 1662 genes were upregulated and 2155 genes were downregulated after inoculation with 107 spores/mL of the HT-1 strain. This strain induced significant upregulation of related genes in the phenylpropanoid biosynthesis pathway, plant hormone signal transduction pathway, biosynthesis of secondary metabolites pathway, and plant-pathogen interaction pathway in R. palmatum. The gene expression trends were revealed through quantitative real-time polymerase chain reaction (qRT-PCR) and were consistent with those determined by RNA-seq. Our results will help us to understand the growth-promoting mechanisms of the HT-1 strain on R. palmatum and provide a theoretical basis for the application of T. citrinoviride HT-1 as a biological fertilizer.

UNASSIGNED: The global attention to the capacities of traditional medicine for alleviating the clinical manifestations of COVID-19 has been growing. The present trial aimed to evaluate the efficacy and safety of a Persian herbal medicine formula among patients with COVID-19.
UNASSIGNED: The present trial was conducted in Afzalipour hospital, Kerman, Iran, from June to September 2020. Hospitalized COVID-19 patients were randomly divided into intervention (Persian herbal medicine formula + routine treatment) or control (only routine treatment) groups. The intervention group received both capsule number 1 and 2 every 8 hours for 7 days. Capsule number 1 contained extract of the Glycyrrhiza glabra, Punica granatum, and Rheum palmatum, and the second capsule was filled by Nigella sativa powder. Participants were followed up to 7 days. The primary outcome was the number of hospitalization days, while cough, fever, and respiratory rate, days on oxygen (O2) therapy, and mortality rate were considered as the secondary outcomes.
UNASSIGNED: Eighty-two patients were enrolled to the study, while 79 cases completed the trial and their data were analyzed (mean age: 59.1 ± 17.1 years). Based on the results, the Persian medicine formula decreased the mean hospitalization days, so that the mean difference of length of hospitalization as primary outcome was 2.95 ± 0.43 days. A significant clinical improvement was observed regarding dyspnea, need for O2) therapy, and respiratory rate in the intervention group. No adverse effects were reported.
UNASSIGNED: The present study supported the use of the Persian medicine formula as an adjuvant therapy for hospitalized COVID-19 patients. Study registration: Iranian Registry of Clinical Trials (www.irct.ir): IRCT20200330046899N1.
UNASSIGNED: Iranian Registry of Clinical Trials (www.irct.ir): IRCT20200330046899N1.

Periodontitis and peri-implantitis are inflammatory conditions with a high global prevalence. Oral pathogens such as Porphyromonas gingivalis play a crucial role in the development of dysbiotic biofilms associated with both diseases. The aim of our study was to identify plant-derived substances which mainly inhibit the growth of \"disease promoting bacteria\", by comparing the effect of Rheum palmatum root extract against P. gingivalis and the commensal species Streptococcus oralis. Antiplanktonic activity was determined by measuring optical density and metabolic activity. Antibiofilm activity was quantified using metabolic activity assays and live/dead fluorescence staining combined with confocal laser scanning microscopy. At concentrations of 3.9 mg/L, R. palmatum root extract selectively inhibited planktonic growth of the oral pathogen P. gingivalis, while not inhibiting growth of S. oralis. Selective effects also occurred in mature biofilms, as P. gingivalis was significantly more stressed and inhibited than S. oralis. Our studies show that low concentrations of R. palmatum root extract specifically inhibit P. gingivalis growth, and offer a promising approach for the development of a potential topical agent to prevent alterations in the microbiome due to overgrowth of pathogenic P. gingivalis.

Novel plant-derived antimicrobials are of interest in dentistry, especially in the treatment of periodontitis, since the use of established substances is associated with side effects and concerns of antimicrobial resistance have been raised. Thus, the present study was performed to quantify the antimicrobial efficacy of crude plant extracts against Porphyromonas gingivalis, a pathogen associated with periodontitis. The minimal inhibitory concentrations (MICs) of Eucalyptus globulus leaf, Azadirachta indica leaf, Glycyrrhiza glabra root and Rheum palmatum root extracts were determined by broth microdilution for P. gingivalis ATCC 33277 according to CLSI (Clinical and Laboratory Standards Institute). The MICs for the E. globulus, A. indica and G. glabra extracts ranged from 64 mg/L to 1024 mg/L. The lowest MIC was determined for an ethanolic R. palmatum extract with 4 mg/L. The MIC for the anthraquinone rhein was also measured, as the antimicrobial activity of P. palmatum root extracts can be partially traced back to rhein. Rhein showed a remarkably low MIC of 0.125 mg/L. However, the major compounds of the R. palmatum root extract were not further separated and purified. In conclusion, R. palmatum root extracts should be further studied for the treatment of periodontitis.