Alleviating the Intestinal Absorption of Rhein in Rhubarb through Herb Compatibility in Tiaowei Chengqi Tang in Caco‐2 Cells

Peng, Ying; Fan, Min; Peng, Cheng; Wang, Mengyue; Li, Xiaobo

doi:10.1155/2018/7835128

Cited by 13 publications

(5 citation statements)

References 20 publications

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“…Therefore, it exists in two forms: Non-dissociation and dissociation. It is considered that the non-dissociation form of Rhein penetrates the cell membrane by active diffusion ( 29 ). When levels of the non-dissociation form of Rhein are reduced, the dissociation form of Rhein turns into the non-dissociation form.…”

Section: Discussionmentioning

confidence: 99%

Dynamic influence of Rhein lysinate on HeLa cells

et al. 2018

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In a previous study, it was demonstrated that Rhein lysinate (RHL) inhibited HeLa cell proliferation via a specific mechanism. The aim of the present study was to clarify the mechanism of RHL by investigating its effect on mitochondrial damage and cell apoptosis. The results indicated that RHL inhibited cell growth and proliferation in HeLa cells. HeLa cells treated with RHL developed extensive vacuolization in a dose- and time-dependent manner. Ultrastructure analysis using transmission electron microscopy revealed that the vacuoles observed were damaged mitochondria and endoplasmic reticulum. The effects of RHL on mitochondria were further confirmed by a decrease in mitochondrial membrane potential and increased generation of reactive oxygen species. The mitochondrial proteome was analyzed, and the results demonstrated that the expression of the cytoskeletal protein keratin and dermal papilla derived protein 12 (associated with the oxidation- reduction process), which are associated with mitochondrial structure and function, were decreased compared with the untreated control group. Hoechst staining, flow cytometry and western blotting also revealed that apoptosis was induced at 24 h following RHL treatment. These results confirm that RHL toxicity in HeLa cells is a dynamic process. Vacuolar degeneration appeared in HeLa cells treated with 160 µmol/l RHL during the first 6 h and with the extension of RHL treatment, cell apoptosis was presented at ~24 h in HeLa cells.

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Section: Discussionmentioning

confidence: 99%

Dynamic influence of Rhein lysinate on HeLa cells

et al. 2018

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“…gastrointestinal tract [13]. The intestinal absorption barrier is a major factor that controls the absorption and oral bioavailability of drugs [14][15][16] and the first steps of pharmacokinetics occur after oral intake. Therefore, exploration of the intestinal absorption mechanism of morroniside is necessary not only for an in vivo pharmacokinetics study but also to provide key information about its effective delivery system.…”

Section: Plos Onementioning

confidence: 99%

Characterization of the intestinal absorption of morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 cell monolayer model

Zhu

et al. 2020

PLoS ONE

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Morroniside is a biologically active polyphenol found in Cornus officinalis Sieb. et Zucc (CO) that exhibits a broad spectrum of pharmacological activities, such as protecting nerves, and preventing diabetic liver damage and renal damage. However, little data are available regarding the mechanism of its intestinal absorption. Here, an in vitro human intestinal epithelial cell model of cultured Caco-2 cells was applied to study the absorption and transport of morroniside. The effects of donor concentration, pH and inhibitors were investigated. The bidirectional permeability of morroniside from the apical (AP) to the basolateral (BL) side and in the reverse direction was studied. When administered at three tested concentrations (5, 25 and 100 μM), the apparent permeability coefficient (P app ) values in the AP-to-BL direction ranged from 1.59 × 10 −6 to 2.66 × 10 −6 cm/s. In the reverse direction, BL-to-AP, the value was ranged from 2.67 × 10 −6 to 4.10 × 10 −6 cm/s. The data indicated that morroniside transport was pH-dependent. The permeability of morroniside was affected by treatment with various inhibitors, such as multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. The mechanisms of the intestinal absorption of morroniside may involve multiple transport pathways, such as the passive diffusion and efflux protein-mediated active transport especially involving multidrug resistance protein 2 and breast cancer resistance protein. After the addition of CO, the P app values in the AP-to-BL direction increased significantly, therefore, it can be assumed that some ingredients in the CO promote morroniside absorption in the small intestine.

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“…f. (M. Li, Wang, et al, 2020). The Tiao Wei Cheng Qi Tang compound has been observed to mitigate the intestinal absorption of rhein, consequently alleviating the toxicity associated with Rheum L. in vitro (Peng et al, 2018). Nux‐vomica is frequently combined with Radix Glycyrrhiza glabra L., Caesalpinia sappan L., Paeonia L., and other herbal medicines to mitigate its toxicity, as noted in previous studies (Gu et al, 2014; Guo et al, 2018; X. D. Liang & Tang, 2014).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the mechanism of nephrotoxicity of nux‐vomica by PTGS2/CYP2C9‐mediated arachidonic acid pathway and Jian Pi Tong Luo compound's protective effect

Zhang,

An,

Zhao

et al. 2024

Biomedical Chromatography

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The clinical effectiveness of nux‐vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme‐linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux‐vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra‐high‐performance liquid chromatography–quadrupole‐time‐of‐flight–MS (UPLC–Q‐TOF–MS), was applied to elucidate the alterations in small‐molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux‐vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux‐vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux‐vomica activating the “PTGS2/CYP2C9–phosphatidylcholine–arachidonic acid metabolic pathway.” This study establishes a scientific foundation for the clinical use of nux‐vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.

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Alleviating the Intestinal Absorption of Rhein in Rhubarb through Herb Compatibility in Tiaowei Chengqi Tang in Caco‐2 Cells

Cited by 13 publications

References 20 publications

Dynamic influence of Rhein lysinate on HeLa cells

Dynamic influence of Rhein lysinate on HeLa cells

Characterization of the intestinal absorption of morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 cell monolayer model

Investigation of the mechanism of nephrotoxicity of nux‐vomica by PTGS2/CYP2C9‐mediated arachidonic acid pathway and Jian Pi Tong Luo compound's protective effect

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