Bioavailability enhancement of osthole after oral administration of Bushen Yizhi prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits extract in comparison to pure osthole at different doses

Zhang, Lei; Yan, Rong; Su, Ruyu; Yang, Cong; Liu, Sijun; Yu, Xin; Chang, Xiang; Zhang, Shijie; Liu, Changhui; Xu, Meili; Zeng, Wu; Chen, Yunbo; Wang, Qi

doi:10.1016/j.jep.2013.09.045

Cited by 26 publications

(8 citation statements)

References 31 publications

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“…As shown in a recent pharmacokinetic study, the bioavailability of osthole was dramatically enhanced after oral administration of BSYZ extract when compared with oral administration of pure osthole. 53 After BSYZ administration, the typical dose-response effect was not observed in the present study. Although significant improvements of object memory were observed in all BSYZ groups, it was noteworthy that compared to the other two groups, BSYZ at medium dose did not have a significant effect on ameliorating spatial memory and regulating NGF signaling in the hippocampus.…”

Section: Discussioncontrasting

confidence: 69%

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Hou

Zhang

Yang

et al. 2015

Rejuvenation Research

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This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.

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Section: Discussioncontrasting

confidence: 69%

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Hou

Zhang

Yang

et al. 2015

Rejuvenation Research

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“…It is also important to note that coexisting constituents in herbal extracts can interact with inducers or inhibitors of cytochrome enzymes. 21) The results reported herein provide important information for studying PA drug interactions in vivo. PA has been shown to be effective at inhibiting phospholipase A2, preventing tumor cell growth, inhibiting DNA topoisomerase II, and exhibiting anti-emetic activity.…”

Section: Discussionmentioning

confidence: 77%

Determination and Pharmacokinetic Study of Pachymic Acid by LC-MS/MS

Wang

Liang

2015

Biological & Pharmaceutical Bulletin

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Poria cocos is a well-known medicinal plant widely used in China and other East Asian countries owing to its various therapeutic effects. Pachymic acid (PA) is a bioactive lanostrane-type triterpenoid from Poria cocos. In this paper, a method of high-performance liquid chromatographic (LC) coupled with triple quadrupole tandem mass spectrometry (QQQ-MS/MS) was developed and validated to investigate the concentration of PA in rat plasma. Samples were prepared by a liquid-liquid extraction, and chromatographic separation was achieved with a Phenomenex Gemini C 18 column (50 mm 2.0 mm i.d.) using a mobile phase consisting of acetonitrile and 0.05% formic acid (85 : 15, v/v) at a flow rate of 0.3 mL/min. The detection was performed on an Applied Bio-Systems API 4000 MS/MS with an electrospray ionization (ESI) inlet in negative multiple reaction monitoring (MRM) mode. Standard curves of samples in plasma were linear (R 2 0.9948) over the concentration range of 5-500 ng/mL, and acceptable accuracy and precision were achieved. The lower limit of quantification and detection were 5 and 0.5 ng/mL, respectively. The method was used successfully to study the pharmacokinetics of PA in rats for oral administration. The main pharmacokinetic parameters of elimination half-life (t 1/2 ), area under the plasma concentration-time curve from time zero to infinity (AUC 0→∞ ), plasma clearance (CL), and apparent volume of distribution (V d ) for the PA group were 4.96 1.33 h, 1466.9 361.7 ng·h/mL, 6.82 1.73 L/h, and 48.85 9.47 L, respectively. This LC-MS/MS method can be developed further for clinical investigation of PA-containing products. Key words Poria cocos; pachymic acid; quantitation; rat plasma; pharmacokinetics; LC-MS/MSBecause of their low toxicities and high levels of effectiveness against many diseases, traditional Chinese medicines (TCMs) have played an important role in the health of the Chinese people for thousands of years. In addition, they have gained ever-increasing global attention owing to the desirability of their bioactive compounds for the discovery of novel drug candidates. Poria cocos, which is also known as Fu Ling, is often used in TCM for its diuretic and sedative effects. 1) P. cocos alone or in combination with other herbs is often used to treat diabetes as well as other disorders. 2-4)The main ingredients of this herbal medicine include a group of triterpenoid compounds. Pachymic acid (PA) is one of the major components in P. cocos and plays an important role in various pharmacological effects. For example, PA has shown anti-inflammatory, 5)anti-apoptotic, and anti-immunologic rejection effects.6) In addition, it has exhibited cytotoxicity against a human colon carcinoma cell line.1,7) Furthermore, PA has been shown to induce apoptosis of human prostate cancer cells by reducing prostaglandin synthesis and AKT activity, 8,9) to stimulate glucose uptake, 10) and to inhibit the phospholipase A2 family of arachidonic acid-producing enzymes.11) Therefore, further pharmacodynamic and pharmacokinetic studie...

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“…Our findings explain why the acute oral toxicity of the Coptidis Rhizoma extract decreased after purification. As mentioned above 8 9 10 11 12 13 14 , the pharmacokinetic properties of some pure active compounds in other natural products are also markedly different from that of crude extracts. We believe that the results of our studies will encourage more related studies.…”

Section: Discussionmentioning

confidence: 99%

“…According to the theory of multi-target therapeutics 5 , the pharmacological effects of natural products may not be caused by a single compound, but instead may be a result of the synergistic combination of the constituents 6 7 . On the other hand, constituents of natural products may enhance the effects of active compounds by improving their pharmacokinetic properties 8 9 10 11 12 13 14 . However, the detailed mechanisms underlying the synergistic effects of natural product constituents remain to be elucidated for most natural products with therapeutic uses.…”

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confidence: 99%

Naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption

Yin

Zhang

et al. 2016

Sci Rep

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Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of Coptidis Rhizoma extract after purification. The water solubility, in vitro absorption, and plasma exposure of berberine (the major active compound) in the Coptidis Rhizoma extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products.

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Bioavailability enhancement of osthole after oral administration of Bushen Yizhi prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits extract in comparison to pure osthole at different doses

Cited by 26 publications

References 31 publications

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Determination and Pharmacokinetic Study of Pachymic Acid by LC-MS/MS

Naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption

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