Rheum tanguticum Alleviates Cognitive Impairment in APP/PS1 Mice by Regulating Drug-Responsive Bacteria and Their Corresponding Microbial Metabolites

Drugs targeting intestinal bacteria have shown great efficacy for alleviating symptoms of Alzheimer’s disease (AD), and microbial metabolites are important messengers. Our previous work indicated that Rheum tanguticum effectively improved cognitive function and reshaped the gut microbial homeostasis in AD rats. However, its therapeutic mechanisms remain unclear. Herein, this study aimed to elaborate the mechanisms of rhubarb for the treatment of AD by identifying effective metabolites associated with rhubarb-responsive bacteria. The results found that rhubarb reduced hippocampal inflammation and neuronal damage in APP/PS1 transgenic (Tg) mice. 16S rRNA sequencing and metabolomic analysis revealed that gut microbiota and their metabolism in Tg mice were disturbed in an age-dependent manner. Rhubarb-responsive bacteria were further identified by real-time polymerase chain reaction (RT-PCR) sequencing. Four different metabolites reversed by rhubarb were found in the position of the important nodes on rhubarb-responsive bacteria and their corresponding metabolites combined with pathological indicators co-network. Furthermore, in vitro experiments demonstrated o-tyrosine not only inhibited the viabilities of primary neurons as well as BV-2 cells, but also increased the levels of intracellular reactive oxygen species and nitric oxide. In the end, the results suggest that rhubarb ameliorates cognitive impairment in Tg mice through decreasing the abundance of o-tyrosine in the gut owing to the regulation of rhubarb-responsive bacteria. Our study provides a promising strategy for elaborating therapeutic mechanisms of bacteria-targeted drugs for AD.

Non-target metabolomics revealed the differences between Rh. tanguticum plants growing under canopy and open habitats

Background Rheum tanguticum (Rh. tanguticum) is an important traditional Chinese medicine plant, “Dahuang”, which contains productive metabolites and occupies wide habitats on the Qinghai-Tibet plateau. Plants occupying wide habitats usually vary in phenotypes such as in morphology and metabolism, thereby developing into different ecotypes. Under canopy and open habitats are a pair of dissimilar habitats which possess Rh. tanguticum plants. However, few studies have focused on the effect of habitats on Rh. tanguticum growth, particularly combining morphological and metabolic changes. This study focused on Rh. tanguticum plants growing in under canopy and open habitats where morphology and metabolism changes were quantified using non-target metabolism methods. Results The obtained results indicated that the two dissimilar habitats led to Rh. tanguticum developing into two distinct ecotypes where the morphology and metabolism were simultaneously changed. Under canopy habitats bred morphologically smaller Rh. tanguticum plants which had a higher level of metabolites (22 out of 31) which included five flavonoids, four isoflavonoids, and three anthracenes. On the other hand, the open habitats produced morphologically larger Rh. tanguticum plants having a higher level of metabolites (9 out of 31) including four flavonoids. 6 of the 31 metabolites were predicted to have effect targets, include 4 represent for under canopy habitats and 2 for open habitats. Totally, 208 targets were connected, among which 42 were communal targets for both under canopy and open habitats represent compounds, and 100 and 66 were unique targets for under canopy superior compounds and open habitats superior compounds, respectively. In addition, aloe-emodin, emodin, chrysophanol, physcion, sennoside A and sennoside B were all more accumulated in under canopy habitats, and among which aloe-emodin, emodin, chrysophanol and physcion were significantly higher in under canopy habitats. Conclusions This study determined that Rh. tanguticum growing in under canopy and in open habitats developed into two distinct ecotypes with morphological and metabolic differences. Results of network pharmacology study has indicated that “Dahuang” coming from different habitats, such as under canopy and open habitats, are different in effect targets and thus may have different medicinal use. According to target metabolomics, under canopy habitats may grow better “Dahuang”.

Polysaccharides extracted from Rheum tanguticum ameliorate radiation-induced enteritis via activation of Nrf2/HO-1

ABSTRACT Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. The Nrf2/HO-1 pathway is a critical endogenous antioxidant stress pathway, but its precise role in radiation-induced enteritis remains to be clarified. Polysaccharides extracted from Rheum tanguticum (RTP) can protect the intestinal cells from radiation-induced damage, but the underlying mechanism is unknown. SD rats and IEC-6 cells were exposed to 12 or 10 Gy X-ray radiation. Rat survival, and histopathological and immunohistochemical profiles were analyzed at different time points. Indicators of oxidative stress and inflammatory response were also assessed. Cell viability, apoptosis and Nrf2/HO-1 expression were evaluated at multiple time points. Significant changes were observed in the physiological and biochemical indexes of rats after radiation, accompanied by significant oxidative stress response. The mRNA and protein expression of Nrf2 peaked at 12 h after irradiation, and HO-1 expression peaked at 48 h after irradiation. RTP administration reduced radiation-induced intestinal damage, upregulated Nrf2/HO-1, improved physiological indexes, significantly decreased apoptosis and inflammatory factors, and upregulated HO-1, particularly at 48 h after irradiation. In conclusion, Nrf2 is activated in the early stage of radiation-induced intestinal injury and plays a protective role. RTP significantly ameliorates radiation-induced intestinal injury via the regulation of Nrf2 and its downstream protein HO-1.

A green strategy for obtaining anthraquinones from Rheum tanguticum by subcritical water

Rheum tanguticum is a traditional Chinese herbal medicine, which contains abundant anthraquinones. In this study, anthraquinones were efficiently extracted from Rheum tanguticum by subcritical water extraction (SWE). The parameters of extraction time (33–67 min), temperature (100–200°C), and SW flow rate (1.4–4.6 mL/min) were optimized so as to achieve a high yield of the target product. A high yield of the total anthraquinones was achieved under the optimized SWE conditions of extraction time 54 min, extraction temperature 170°C, and the flow rate 2.0 mL/min. The comparison between the SWE and traditional extraction techniques implied that the SWE is an efficient and green alternative method for the extraction of anthraquinones. Four anthraquinone glycosides were purified from the SWE extract by high-speed counter-current chromatography and identified as emodin-1-O-β-D-glucoside, physcion-8-O-β-D-glucopyranoside, chrysophanol-1-O-β-D-glucoside, and chrysophanol-8-O-β-D-glucoside.

Thermoregulation adaptation of Rheum tanguticum stereostructure leaf

Background: Leaf is an important plant organ with great variation in shape and size. Leaf size tends to be smaller in plants thrived in the areas of higher elevation and lower annual mean temperature. The Qinghai-Tibetan Plateau is situated at a high altitude of ＞4,000 m with low annual average temperature. Leaves for most plants species in Qinghai-Tibetan Plateau are small, however, Rheum tanguticum with large leaves is an exception. Here we show that large leaf of R. tanguticum with three-dimensional structure is an ideal solution of thermoregulation with little energy consumption.Results: With increase in age, leaves of R. tanguticum transit from a small oval plane to a large palmatipartite stereostructure. Furthermore, temperature variation of different parts is a distinct character in stereostructure leaves of R. tanguticum. The temperature of regular leaves under strong solar radiation could be much higher than the ambient temperature. However, the stereostructure leaf could lower leaf temperature by avoiding the direct solar radiation and promoting local airflow to prevent serious scorch.Conclusions: Our results demonstrate that the robust three-dimensional leaf structure is a formation for R. tanguticum to adapt to the strong solar radiation and low temperature in Qinghai-Tibetan Plateau through modulation of local temperature in different parts of the large leaves.