Pharmacokinetic Compatibility of Ginsenosides and Schisandra Lignans in Shengmai-san: From the Perspective of P-Glycoprotein

Liang, Yan; Zhou, Yuanyuan; Zhang, Jingwei; Rao, Tai; Zhou, Lijun; Rong, Xing; Wang, Qian; Fu, Hanxu; Hao, Kun; Xie, Lin; Wang, Guangji

doi:10.1371/journal.pone.0098717

Cited by 33 publications

(20 citation statements)

References 33 publications

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“…The minister drug helps strengthen the curative effect of the monarch drug, or, is used for treatment of accompanying symptoms [41]. The assistant drug is used to promote the treatment efficacy of the minister drug on chief syndromes/disease, or to aim at minor symptoms [42]. The Guide drug is to lead the ‘herbs’ impact to the disease location and to modulate the interaction among the herbs [43].…”

Section: Resultsmentioning

confidence: 99%

A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines

Li¹,

Wang²,

Feng³

et al. 2017

PLoS ONE

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Breast cancer is the most common carcinoma in women. Comprehensive therapy on breast cancer including surgical operation, chemotherapy, radiotherapy, endocrinotherapy, etc. could help, but still has serious side effect and resistance against anticancer drugs. Complementary and alternative medicine (CAM) may avoid these problems, in which traditional Chinese medicine (TCM) has been highlighted. In this section, to analyze the mechanism through which TCM act on breast cancer, we have built a virtual model consisting of the construction of database, oral bioavailability prediction, drug-likeness evaluation, target prediction, network construction. The 20 commonly employed herbs for the treatment of breast cancer were used as a database to carry out research. As a result, 150 ingredient compounds were screened out as active molecules for the herbs, with 33 target proteins predicted. Our analysis indicates that these herbs 1) takes a ‘Jun-Chen-Zuo-Shi” as rule of prescription, 2) which function mainly through perturbing three pathways involving the epidermal growth factor receptor, estrogen receptor, and inflammatory pathways, to 3) display the breast cancer-related anti-estrogen, anti-inflammatory, regulation of cell metabolism and proliferation activities. To sum it up, by providing a novel in silico strategy for investigation of the botanical drugs, this work may be of some help for understanding the action mechanisms of herbal medicines and for discovery of new drugs from plants.

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Section: Resultsmentioning

confidence: 99%

A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines

Li¹,

Wang²,

Feng³

et al. 2017

PLoS ONE

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“… 26 Located in the apical membrane of several barrier epithelia, including the intestine, renal epithelial cells, bile canalicula, and the brain capillary endothelial cells, P-gp’s inhibition or induction may be responsible for drug interactions with phytomedicines. 27 Changes in the levels of P-gp were measured in renal tissue by Western blotting assay. The results showed that P-gp level was intensively increased when rats were exposed to CsA when compared with vehicle control rats ( Figure 10 , P <0.001).…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Lai¹,

Wei²,

Mahmoodurrahman³

et al. 2015

DDDT

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Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting from its long-term usage has hampered its prolonged therapeutic usage. Schisandra chinensis extracts (SCE) have previously been used in traditional Chinese medicine and more recently coadministered with Western medicine for the treatment of CsA-induced side effects in the People’s Republic of China. This study aimed to investigate the possible effects of SCE on the pharmacokinetics of CsA in rats and elucidate the potential mechanisms by which it hinders the development of CsA-induced nephrotoxicity. A liquid chromatography/tandem mass spectrometry method was developed and validated for determining the effect of SCE on the pharmacokinetics of CsA. Male Sprague Dawley rats, which were administered with CsA (25 mg/kg/d) alone or in combination with SCE (54 mg/kg/d and 108 mg/kg/d) for 28 days, were used to evaluate the nephroprotective effects of SCE. Our study showed that SCE increased the mean blood concentration of CsA. Furthermore, we found that the concomitant administration of SCE alongside CsA prevented the disruption of catalase activity and reduction in creatinine, urea, renal malondialdehyde, and glutathione peroxidase levels that would have otherwise occurred in the absence of SCE administration. SCE treatment markedly suppressed the expression of 4-hydroxynonenal, Bcl-2-associated X protein, cleaved caspase 3, and autophagy-related protein LC3 A/B. On the other hand, the expression of heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf2), and P-glycoprotein was enhanced by the very same addition of SCE. SCE was also able to increase the systemic exposure of CsA in rats. The renoprotective effects of SCE were thought to be mediated by its antiapoptotic and antioxidant abilities, which caused the attenuation of CsA-induced autophagic cell death. All in all, these findings suggest the prospective use of SCE as an effective adjunct in a CsA-based immunosuppressive regimen.

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“…al. have showed that the e ux ratios of some ginsenosides, e.g., Rh1, F1, Re, and Rg1, were not affected by verapamil (48). This may be due to the different structures of ginsenosides and existence of other transporters involved in the absorption of certain ginsenosides.…”

Section: Discussionmentioning

confidence: 99%

Chemoprevention of Lung Carcinogenesis by Red Ginseng and Ginsenoside Rg3 in A/J mice

Xiong

Yuan

Fei

et al. 2020

Preprint

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Background: Red ginseng has long been used as a traditional medicine for a variety of maladies. Ginsenosides are the active components of ginseng but are limited by their low oral bioavailability. Methods: We evaluated several types of red ginseng extracts for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene [B(a)P] in A/J mice. The concentrations of various ginsenosides were quantified in these ginseng extracts using the methods of ultra-performance liquid chromatography tandem mass spectrometry analysis to identify the ginsenosides that may contribute to cancer prevention. We next explored whether inhibition of P-glycoprotein by verapamil could increase the oral bioavailability of ginsenoside by using CaCo-2 cell transcellular transport and in situ mouse intestinal perfusion models. The plasma and intestine concentration of ginsenoside and cancer preventive effect of ginsenoside combined with verapamil in A/J mice were also detected by using B(a)P-induced mouse cancer model.Results: We found that treatment with one type of red ginseng (Korean red ginseng B, KRGB) led to a significant reduction of tumor load compared with other types of red ginseng. KRGB contained the highest concentration of ginsenoside Rg3 among these red ginseng extracts, suggested that Rg3 may play an important role in its preventive efficacy. Our study showed that Rg3 had a relatively poor bioavailability, and co-administration of verapamil decreased the efflux ratio of Rg3 in Caco-2 cells, increased the absorption rate of Rg3 in rat small intestine, increased the plasma and intestine concentration of Rg3 in A/J mice, and enhanced the cancer preventive effect of Rg3 against B(a)P induced lung tumorigenesis. Conclusions: Ginsenosides Rg3 is one of the key components of read ginseng that may be responsible for its efficacy against lung carcinogenesis in mice. Rg3 appears to be the substrate of P-glycoprotein, and inhibition of P-glycoprotein could enhance its oral bioavailability.

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Pharmacokinetic Compatibility of Ginsenosides and Schisandra Lignans in Shengmai-san: From the Perspective of P-Glycoprotein

Cited by 33 publications

References 33 publications

A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines

A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

Chemoprevention of Lung Carcinogenesis by Red Ginseng and Ginsenoside Rg3 in A/J mice

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