L-tetrahydropalmatine attenuates cisplatin-induced nephrotoxicity via selective inhibition of organic cation transporter 2 without impairing its antitumor efficacy

Li, Cui; Li, Liping; Yi, Yaodong; Wang, Wei; Yuan, Jingqun; Tan, Fu-Qing; Fang, Danbo; Zeng, Su; Zhou, Hui; Jiang, Huidi

doi:10.1016/j.bcp.2020.114021

Cited by 14 publications

(7 citation statements)

References 44 publications

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“…In ovarian cancer A2780/DDP cell line, THP can increase the sensitivity of ovarian cancer cells to cisplatin by regulating the miR-93/PTEN/AKT pathway ( Gong et al, 2019 ). Moreover, THP alleviates kidney injury induced by cisplatin through the selective inhibition of organic cation transporter 2 (OCT2) but does not affect its antitumor effect ( Li et al, 2020 ). THP can inhibit the uptake of oxaliplatin (OXA), which has severe peripheral neurotoxicity ( Yi et al, 2021 ).…”

Section: Pharmacological Activities Of Tetrahydropalmatinementioning

confidence: 99%

A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine

Meng

Wang

2022

Front. Pharmacol.

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Tetrahydropalmatine (THP), a tetrahydroproberine isoquinoline alkaloid, is widely present in some botanical drugs, such as Stephania epigaea H.S. Lo (Menispermaceae; Radix stephaniae epigaeae), Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su and C.Y. Wu (Papaveraceae; Corydalis rhizoma), and Phellodendron chinense C.K.Schneid (Berberidaceae; Phellodendri chinensis cortex). THP has attracted considerable attention because of its diverse pharmacological activities. In this review, the chemical properties, plant sources, pharmacological activities, pharmacokinetic and toxicological characteristics of THP were systematically summarized for the first time. The results indicated that THP mainly existed in Papaveraceae and Menispermaceae families. Its pharmacological activities include anti-addiction, anti-inflammatory, analgesic, neuroprotective, and antitumor effects. Pharmacokinetic studies showed that THP was inadequately absorbed in the intestine and had rapid clearance and low bioavailability in vivo, as well as self-microemulsifying drug delivery systems, which could increase the absorption level and absorption rate of THP and improve its bioavailability. In addition, THP may have potential cardiac and neurological toxicity, but toxicity studies of THP are limited, especially its long-duration and acute toxicity tests. In summary, THP, as a natural alkaloid, has application prospects and potential development value, which is promising to be a novel drug for the treatment of pain, inflammation, and other related diseases. Further research on its potential target, molecular mechanism, toxicity, and oral utilization should need to be strengthened in the future.

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Section: Pharmacological Activities Of Tetrahydropalmatinementioning

confidence: 99%

A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine

Meng

Wang

2022

Front. Pharmacol.

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“…Low doses of rotundine produced no side effects in mice and relieved pain in patients [ 40 ]. 40 mg/kg rotundine selectively inhibited OCT2 to reduce renal injury without impairing anti-tumor function [ 41 ]. In much Chinese literature, adverse reactions in clinical trials of rotundine include nausea, vomiting, dizziness, chest tightness, and weakness.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing Reveals That Rotundine Inhibits Colorectal Cancer by Regulating Prognosis-Related Genes

Huang

Zou

Liang

et al. 2023

JPM

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Background: Rotundine is an herbal medicine with anti-cancer effects. However, little is known about the anti-cancer effect of rotundine on colorectal cancer. Therefore, our study aimed to investigate the specific molecular mechanism of rotundine inhibition of colorectal cancer. Methods: MTT and cell scratch assay were performed to investigate the effects of rotundine on the viability, migration, and invasion ability of SW480 cells. Changes in cell apoptosis were analyzed by flow cytometry. DEGs were detected by high-throughput sequencing after the action of rotundine on SW480 cells, and the DEGs were subjected to function enrichment analysis. Bioinformatics analyses were performed to screen out prognosis-related DEGs of COAD. Followed by enrichment analysis of prognosis-related DEGs. Furthermore, prognostic models were constructed, including ROC analysis, risk curve analysis, PCA and t-SNE, Nomo analysis, and Kaplan–Meier prognostic analysis. Results: In this study, we showed that rotundine concentrations of 50 μM, 100 μM, 150 μM, and 200 μM inhibited the proliferation, migration, and invasion of SW480 cells in a time- and concentration-dependent manner. Rotundine does not induce SW480 cell apoptosis. Compared to the control group, high-throughput results showed that there were 385 DEGs in the SW480 group. And DEGs were associated with the Hippo signaling pathway. In addition, 16 of the DEGs were significantly associated with poorer prognosis in COAD, with MEF2B, CCDC187, PSD2, RGS16, PLXDC1, HELB, ASIC3, PLCH2, IGF2BP3, CLHC1, DNHD1, SACS, H1-4, ANKRD36, and ZNF117 being highly expressed in COAD and ARV1 being lowly expressed. Prognosis-related DEGs were mainly enriched in cancer-related pathways and biological functions, such as inositol phosphate metabolism, enterobactin transmembrane transporter activity, and enterobactin transport. Prognostic modeling also showed that these 16 DEGs could be used as predictors of overall survival prognosis in COAD patients. Conclusions: Rotundine inhibits the development and progression of colorectal cancer by regulating the expression of these prognosis-related genes. Our findings could further provide new directions for the treatment of colorectal cancer.

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“…The protective effect of THP against organ injury has been largely reported in liver (Q. Yu et al, 2018), kidney (C. Li, Li et al, 2020), and brain (R. Sun, Song et al, 2018). Jing et al demonstrated that THP attenuated irradiation‐induced lung injury in rats, indicating the protective effect of THP against lung injury (J. Yu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Tetrahydropalmatine induces the polarization of M1 macrophages to M2 to relieve limb ischemia‐reperfusion‐induced lung injury via inhibiting the TLR4/NF‐κB/NLRP3 signaling pathway

Wen

Chen

et al. 2022

Drug Development Research

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Tetrahydropalmatine (THP) is the main component of the Chinese medicine Corydalis yanhusuo, which has been reported to alleviate limb ischemia‐reperfusion‐induced acute lung injury (LIR‐ALI). This study aimed to investigate the mechanism underlying the effect of THP on relieving LIR‐ALI. LIR‐ALI model was established in rats with the presence or absence of THP pretreatment. Then, BEAS‐2B cells and THP‐1 macrophages were cocultured with rat serum from the Sham group and the Model group in the presence or absence of THP pretreatment. Subsequently, lung/body weight and lung wet/dry ratio of rats were calculated. Histological changes of lung tissues were observed by hematoxylin‐eosin staining. Expression of CD86 and CD163 in lung tissues of rats was assessed by quantitative reverse transcription polymerase chain reaction, immunohistochemistry staining, and flow cytometry analysis. Levels of inflammatory cytokines were measured by enzyme linked immunosorbent assay. The expression of proteins related to toll‐like receptor 4 (TLR4)/nuclear factor‐κB (NF‐κB)/NLRP3 signaling was detected by western blot analysis. Results revealed that THP significantly relieved LIR‐ALI in rats. Moreover, THP also reduced CD86 expression but elevated CD163 expression in lung tissues of rats with LIR‐ALI. Furthermore, THP inhibited inflammation in serum and bronchoalveolar lavage fluid of rats with LIR‐ALI and inactivated the TLR4/NF‐κB/NLRP3 signaling in vivo. Additionally, coculture of serum from rats in the Model group also reduced viability, promoted inflammation, inactivated TLR4/NF‐κB/NLRP3 expression in BEAS‐2B cells and inhibited macrophage polarization, while these effects were all reversed by THP treatment. Collectively, THP could induce the polarization of M1 macrophage to M2 to suppress inflammation via inhibiting TLR4/NF‐κB/NLRP3 signaling, thereby attenuating LIR‐ALI.

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L-tetrahydropalmatine attenuates cisplatin-induced nephrotoxicity via selective inhibition of organic cation transporter 2 without impairing its antitumor efficacy

Cited by 14 publications

References 44 publications

A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine

A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine

High-Throughput Sequencing Reveals That Rotundine Inhibits Colorectal Cancer by Regulating Prognosis-Related Genes

Tetrahydropalmatine induces the polarization of M1 macrophages to M2 to relieve limb ischemia‐reperfusion‐induced lung injury via inhibiting the TLR4/NF‐κB/NLRP3 signaling pathway

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