One-month toxicokinetic study of SHENMAI injection in rats

Yu, Jian; Xin, Yanfei; Gu, Lian‐Quan; Gao, Haiyan; Li-juan, Xia; You, Zhang; Xie, Feng; Ma, Zhu-Feng; Wang, Zhi; Xuan, Yue

doi:10.1016/j.jep.2014.04.014

Cited by 24 publications

(17 citation statements)

References 14 publications

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“…SMI had no significant impact on the ADR and PTX concentrations in the heart, liver and other tissues (Figure 3). In accordance with our results, SMI seems to be generally safe for clinical use [4,6,8,18] . Many studies have found that the synergistic effects of SMI or its main components, ginseng saponins, with chemotherapeutic agents were due to the influence on multiple cancer signaling pathways, such as NF-κB, JNK, MAPK, p53, among others [19,20] .…”

Section: Discussionsupporting

confidence: 92%

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

et al. 2016

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Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg -1 ·3d -1 ) or PTX (7.5 mg·kg -1 ·3d -1 ) with or without SMI (0.01 mL·g -1 ·d -1 ) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 μL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r 2 =+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX.

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Section: Discussionsupporting

confidence: 92%

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

et al. 2016

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“…In addition, the toxicity of SMI has been evaluated and it is generally considered to be safe to use (25,26). 'Shen' and 'mai' are Chinese abbreviations for red ginseng and Ophiopogon japonicas.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Shenmai injection on knee articular cartilage of osteoarthritic rabbits and IL-1β-stimulated human chondrocytes

Yao

Chen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Shenmai injection (SMI) has been widely used as a therapy to treat a number of diseases. However, its anti-osteoarthritic properties have not yet been fully investigated. In the present study, the protective effect of SMI on knee articular cartilage of anterior cruciate ligament transected rabbits and interleukin-1β (IL-1β)-stimulated human chondrocytes was investigated. For the in vivo study, knee osteoarthritis (KOA) was induced in female New Zealand white rabbits by anterior cruciate ligament transection (ACLT) in the knee of right hind limb. Rabbits either underwent sham surgery or ACLT surgery. Out of the rabbits receiving ACLT surgery, half of the rabbits received one 0.3 ml Shenmai intra-articular injection in the knee per week for four weeks, following ACLT surgery. The other rabbits received the same volume of normal saline solution. The cartilage was subsequently collected for histological evaluation. For the in vitro study, cultured human chondrocytes were treated with 10 ng/ml IL-1β in the presence or absence of 5 and 2% (v/v) SMI for 24 h. Nitric oxide (NO) and prostaglandin E2 (PGE2) levels in cell culture supernatant were assessed using a Griess reaction and ELISA respectively.The mRNA expression of cyclooxgenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) in chondrocytes were detected by reverse transcription-quantitative polymerase chain reaction. The results of the current study revealed that treatment with SMI ameliorated cartilage degradation in the ACLT rabbit model, and decreased levels of NO and PGE2. Furthermore, treatment with SMI decreased levels of COX-2, iNOS, MMP-1 and MMP-13 mRNA expression and increased TIMP-1 mRNA expression in IL-1β-stimulated human chondrocytes. These results indicate that SMI suppresses inflammation and ameliorated cartilage degradation, making it a potential and promising therapeutic option to treat KOA.

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“…The SM-I dosage was calculated on based on 5 times the normal clinically used dosage (40 mL per person daily, weight = 60 kg). The rats were injected intraperitoneally with the maximum dose (20 mL/kg/day) according to our previous study and other data [21,22].…”

Section: Animal Preparationmentioning

confidence: 99%

Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating CYP2J3/EETs in Rats

Huang

Wang²,

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase (CYP) metabolites of arachidonic acid and have multiple cardiovascular effects. Ophiopogonin D (OP-D) is an important effective monomeric component in Shenmai injection (SM-I). Both have been reported to have a variety of biological functions, including anti-inflammatory, anti-oxidant, and anti-apoptotic effects. We previously demonstrated that OP-D–mediated cardioprotection involves activation of CYP2J2/3 and enhancement of circulating EETs levels in vitro and can be developed as a novel drug for the therapy of myocardial ischemia-reperfusion (MI/R) injury. We therefore hypothesized that the protective effects of OP-D and SM-I against MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in vivo. Methods: A rat model of MI/R injury was generated by ligation of the left anterior descending coronary artery for 40 min, followed by reperfusion for 2 h to determine the protective effects and potential mechanisms of OP-D and SM-I. Electrocardiogram and ultrasonic cardiogram were used to evaluate cardiac function; 2,3,5-triphenyltetrazolium chloride was used to measure myocardial infarct size; hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of myocardial tissue; and the expression of related proteins in the mechanistic study was observed by western blot analysis. Results: We found that OP-D and SM-I exert protective effects on MI/R injury, including regulation of cardiac function, reduction of lactate dehydrogenase and creatine kinase production, attenuation of myocardial infarct size, and improvement of the recovery of damaged myocardial structures. We found that OP-D and SM-I activate CYP2J3 expression and increase levels of circulating 11,12-EET in MI/R-injured rats. Conclusion: We tested the hypothesis that the cardioprotective effects of OP-D and SM-I on MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in rats. Taken together, our results show that the effects of OP-D and SM-I were also mediated by the activation of the PI3K/Akt/eNOS signaling pathway, while inhibition of the NF-κB signaling pathway and antioxidant and anti-apoptotic effects were involved in the cardioprotective effects of OP-D and SM-I.

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One-month toxicokinetic study of SHENMAI injection in rats

Cited by 24 publications

References 14 publications

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

Protective effect of Shenmai injection on knee articular cartilage of osteoarthritic rabbits and IL-1β-stimulated human chondrocytes

Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating CYP2J3/EETs in Rats

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