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The Mongolian rhubarb—Rheum undulatum L. (RU)—and Rumex crispus L. (RC)—a Taiwanese local rhubarb belonging to the family of Polygonaceae—are principal therapeutic materials in integrative medicine due to their rich quantities of bioactive compounds; however, their phytochemical and antioxidant properties, and anti-cancer activity is poorly investigated. Furthermore, the phytochemical characteristics of both species may be affected by their different geographical distribution and climatic variance. The current study aimed to compare RU with RC extracts in different polarity solvents (n-hexane, ethyl acetate, acetone, ethanol, and water) for their phytochemical contents including the total phenolic content (TPC), total anthraquinone content (TAC), total flavonoid content (TFC), antioxidant and free radical scavenging capacities, and anticancer ability on the HepG2 cell. Except for the n-hexane extract, all of the RU extracts had considerably higher TPCs than RC extracts, ranging from 8.39 to 11.16 mg gallic acid equivalent (GAE) per gram of dry weight, and the TPCs of each extract were also significantly correlated with their antioxidant capacities by ABTS, DPPH, and FRAP assays (p < 0.05). Moreover, there was no remarkable association between the antioxidant capacities and either TACs or TFCs in both the RU and RC extracts. Besides, high-performance liquid chromatography (HPLC) analysis revealed that both the RU and RC extracts contained chrysophanol, emodin, and physcion, and those bioactive compounds were relatively higher in the n-hexane solvent extracts. Additionally, we observed different levels of dose-dependent cytotoxic effects in all the extracts by cell viability assay. Notably, the ethanol extract of RU had a compelling cytotoxic effect with the lowest half-maximum inhibition concentration (IC50-171.94 ± 6.56 µg/mL at 48 h) among the RU extracts than the ethanol extract of RC. Interestingly, the ethanol extract of RU but not RC significantly induced apoptosis in the human liver cancer cell line, HepG2, with a distinct pattern in caspase-3 activation, resulting in increased PARP cleavage and DNA damage. In summary, Mongolian Rhubarb, RU, showed more phytochemical contents, as well as a higher antioxidant capacity and apoptotic effect to HepG2 than RC; thus, it can be exploited for the proper source of natural antioxidants and liver cancer treatment in further investigation.

Rheum undulatum L. (R. undulatum) is a medicinal plant used for the treatment of inflammatory diseases in East Asian countries. Numerous stilbenes isolated from R. undulatum have been revealed to possess anticancer effects. The aim of the present study was to evaluate the effect of extracts and compounds isolated from R. undulatum on human gastric cancer cell viability and to elucidate their molecular mechanism of action on the apoptosis pathway. The results demonstrated that aloe-emodin and chrysophanol 1-O-β-D-glucopyranoside, isolated from the methanolic extract of dried rhizomes of R. undulatum, exhibited anti-proliferative effects on the human gastric carcinoma cell line AGS, with IC50 values of 84.66±0.44 and 68.28±0.29 µM, respectively. The percentage of apoptotic cells increased significantly following treatment with each compound at a concentration of 100 µM, compared with that in the non-treated group in the image-based cytometry assay. Western blot analysis revealed that these compounds activated the caspase cascade and inhibited B-cell lymphoma-2, an anti-apoptotic protein. [ABSTRACT FROM AUTHOR]

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying con¬centrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at 70 μg/mL, 15.94% at 140 μg/mL, 26.56% at 210 μg/mL and 38.08% at 280 μg/mL). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

Although current chemotherapeutic agents are active at the beginning of therapy, the most common risk is the development of resistance during later stages in almost all cancer types including breast cancer. Hence, investigation of novel drugs is still a priority goal for cancer treatment. The objective of the present study is to investigate the anticancer effect of a derivative of stilbene, deoxyrhapontigenin (DR) isolated from Rheum undulatum L. root extracts against the chemoresistant MCF-7/adr and its parental MCF-7 human breast cancer cells. The morphological images indicate that DR induces an extensive cytoplasmic vacuolation in breast cancer cells. Mechanistic investigations revealed that DR treatment causes endoplasmic reticulum (ER) dilation and upregulated the expression of ER stress markers GRP78, IRE1α, eIF2α, CHOP, JNK, and p38. Subsequently, we also identified that DR increases the levels of apoptotic fragment of PARP (89 kDa) in breast cancer cells. Blocking the expression of one of the components of the ER stress–mediated apoptosis pathway, CHOP using siRNA significantly decreased DR-induced apoptotic cleavage of PARP. In summary, the present study suggests that the induction of ER stress–mediated apoptosis by DR may account for its cytotoxic effects in human breast cancer cells. [ABSTRACT FROM AUTHOR]

This research aims to identify the main active compounds of Rhei undulati Rhizoma (roots of Rheum undulatum LINNE) and determine the types of anthraquinones absorbed into the body and their pharmacokinetic parameters. The boiling-water extract of the herb was administered to 12 healthy volunteers (9 men/3 women) at a dosage of 100 mg/kg the anthraquinone levels in plasma were determined with TLC, HPLC, and LC-MS. Rhein was the only anthraquinone compound absorbed by the body as determined for plasma analysis of the volunteers. The elimination rate constant of rhein in Rhei undulati Rhizoma was 0.23±0.02/h and the half life was 3.38±0.35 h. This experiment confirmed that rhein is the most important active compound absorbed by the body among anthraquinones contained in Rhei undulati Rhizoma, indicating that rhein is a promising marker substance to evaluate Rhei Rhizoma and Rhei undulati Rhizoma. [Copyright &y& Elsevier]

The Mongolian rhubarb—Rheum undulatum L. (RU)—and Rumex crispus L. (RC)—a Taiwanese local rhubarb belonging to the family of Polygonaceae—are principal therapeutic materials in integrative medicine due to their rich quantities of bioactive compounds; however, their phytochemical and antioxidant properties, and anti-cancer activity is poorly investigated. Furthermore, the phytochemical characteristics of both species may be affected by their different geographical distribution and climatic variance. The current study aimed to compare RU with RC extracts in different polarity solvents (n-hexane, ethyl acetate, acetone, ethanol, and water) for their phytochemical contents including the total phenolic content (TPC), total anthraquinone content (TAC), total flavonoid content (TFC), antioxidant and free radical scavenging capacities, and anticancer ability on the HepG2 cell. Except for the n-hexane extract, all of the RU extracts had considerably higher TPCs than RC extracts, ranging from 8.39 to 11.16 mg gallic acid equivalent (GAE) per gram of dry weight, and the TPCs of each extract were also significantly correlated with their antioxidant capacities by ABTS, DPPH, and FRAP assays (p < 0.05). Moreover, there was no remarkable association between the antioxidant capacities and either TACs or TFCs in both the RU and RC extracts. Besides, high-performance liquid chromatography (HPLC) analysis revealed that both the RU and RC extracts contained chrysophanol, emodin, and physcion, and those bioactive compounds were relatively higher in the n-hexane solvent extracts. Additionally, we observed different levels of dose-dependent cytotoxic effects in all the extracts by cell viability assay. Notably, the ethanol extract of RU had a compelling cytotoxic effect with the lowest half-maximum inhibition concentration (IC50-171.94 ± 6.56 µg/mL at 48 h) among the RU extracts than the ethanol extract of RC. Interestingly, the ethanol extract of RU but not RC significantly induced apoptosis in the human liver cancer cell line, HepG2, with a distinct pattern in caspase-3 activation, resulting in increased PARP cleavage and DNA damage. In summary, Mongolian Rhubarb, RU, showed more phytochemical contents, as well as a higher antioxidant capacity and apoptotic effect to HepG2 than RC; thus, it can be exploited for the proper source of natural antioxidants and liver cancer treatment in further investigation. [ABSTRACT FROM AUTHOR]

We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells. The activation of apoptosis pathway-related proteins was investigated by western blotting, using extracts of R. undulatum prepared in three solvent conditions (EX1, EX2, and EX3). The R. undulatum chemical constituents (compounds 1–3) showed estrogen-like activity in the concentration range of 10 to 50 μM, by increasing the proliferation of human ER-positive MCF-7 cells. These effects were attenuated by co-treatment with 100 nM fulvestrant, an ER antagonist. Compounds 1–3 decreased the viability of MCF-7 cells in a concentration-dependent manner. Compounds 1 (aloe emodin) and 2 (rhapontigenin) induced mitochondria-independent apoptosis by activating the caspase-8 pathway, whereas the cytotoxic effect of compound 3 (chrysophanol 1-O-β-d-glucopyranoside) was mediated through the mitochondria-dependent apoptotic pathway. [ABSTRACT FROM AUTHOR]