Home | About PM | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Pharmacognosy Magazine
Search Article 
  
Advanced search 
 


 
  Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 67  |  Page : 111-118  

Pharmacokinetic comparisons of six major bioactive components in rats after oral administration of crude and saltwater processed Phellodendri amurensis cortex by ultra-performance liquid chromatography–Mass spectrometry/mass spectrometry


School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China

Date of Submission13-Jun-2019
Date of Decision22-Aug-2019
Date of Web Publication11-Feb-2020

Correspondence Address:
Tian-Zhu Jia
No. 77 Life One Road, Dd Port, Development Zone, 116600 Dalian
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_257_19

Rights and Permissions
   Abstract 


Background: The Phellodendri amurensis cortex is a traditional Chinese medicine with multiple pharmacodymic uses (antibacterial, anti-inflammation, antitumor, etc). It is often processed by saltwater to strengthen its effects in terms of nourishing yin to reduce pathogenic fire and reducing asthenic fever. To clarify the principle of saltwater processing, an experiment of pharmacokinetic comparison after oral administration from crude P. amurensis cortex and its saltwater processed product was carried out. Materials and Methods: A validated and sensitive ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) method was established for simultaneous quantification of five alkaloids and one triterpene in rat. An UPLC C18column was used for chromatograph separation by an elution program with the mobile phase consisting of 0.1% formic acid and acetonitrile. Each analytes and internal standard, nimodipine, was detected using positive ion scan mode via multiple reaction monitoring mode. All of the validation parameters investigated involving selectivity, precision, accuracy, extraction recovery, matrix effects, and stability shown this approach was suitable to the pharmacokinetic study. Results: Pharmacokinetic profiles showed these parameters of maximum of drug concentration and AUC0-tof alkaloids analytes elevated remarkably after oral administration of P. amurensis cortex processed with the saltwater. Conclusion: The results suggested that the absorption effect from the saltwater processed product was better than those from crude product, which could explain that saltwater processing may enhance the activity of clearing heat and removing toxicity from P. amurensis cortex.

Keywords: Alkaloids, pharmacokinetic, Phellodendri amurensis cortex, saltwater processing, ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry


How to cite this article:
Zhang F, Meng L, Liu PP, Shan GS, Jia TZ. Pharmacokinetic comparisons of six major bioactive components in rats after oral administration of crude and saltwater processed Phellodendri amurensis cortex by ultra-performance liquid chromatography–Mass spectrometry/mass spectrometry. Phcog Mag 2020;16:111-8

How to cite this URL:
Zhang F, Meng L, Liu PP, Shan GS, Jia TZ. Pharmacokinetic comparisons of six major bioactive components in rats after oral administration of crude and saltwater processed Phellodendri amurensis cortex by ultra-performance liquid chromatography–Mass spectrometry/mass spectrometry. Phcog Mag [serial online] 2020 [cited 2020 Feb 17];16:111-8. Available from: http://www.phcog.com/text.asp?2020/16/67/111/278009



SUMMARY

  • In our study, an ultra-performance liquid chromatography-mass spectrometry/mass spectrometry approach was established for simultaneous quantitation of five alkaloids and one triterpene from Phellodendri amurensis cortex. The approach was successfully used to investigate pharmacokinetic differences in rats. The result demonstrated that saltwater processing might enhance the absorption of alkaloids from Phellodendri amurensis cortex. It is the first time about the study on comparative pharmacokinetic of crude Phellodendri amurensis cortex and its saltwater processed product and the result could suggest that saltwater processing would strengthen its bioactivity of clearing heat via enhancing the absorption of the alkaloids from Phellodendri amurensis cortex.




Abbreviations used: GHB: Phellodendri amurensis cortex; CGHB: Crude Phellodendri amurensis cortex; SGHB: Saltwater processed Phellodendri amurensis Cortex; HPLC: High-performance liquid chromatography; UPLC-MS/MS: Ultra-performance liquid chromatography-mass spectrometry/mass spectrometry; UPLC-QqQ-MS: Ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry; MRM: Multiple reaction monitoring mode; QC: Quality control; RE: Relative error; RSD: Relative standard deviation; Cmax: Maximum of drug concentration; Tmax: Time for maximum of drug concentration; AUC: Area under concentration-time curve; LLOQ: lower limit of quantification; T½: Half-life.


   Introduction Top


The Phellodendri amurensis cortex, named “Guanhuangbo” (GHB) in Chinese, the dried bark of P. amurensis Rupr. (Family: Rutaceae), has been widely applied for thousands of years in China. In traditional Chinese medicine (TCM), GHB is used to “clear heat, dry dampness, purge fire, relieve steaming, remove toxin, and treat sore.”[1] In clinic, it can be used to treat bacterial malaria, pneumonia, acute conjunctivitis, etc.[2] According to requirements in the science of TCM, most herbs must be processed by a certain method to be used in clinical practice. The purpose of processing is to enhance efficacy, reduce toxic effects, or eliminate side effects. GHB is now often processed by stir-frying with saltwater (SGHB). Compared with crude GHB (CGHB), SGHB can moderate its bitter flavor and drastic properties and strengthen its effects in terms of nourishing yin to reduce pathogenic fire and reducing asthenic fever.[3],[4]

Various bioactive compounds, especially protoberberine-type alkaloids,[5] have been identified in GHB, and most of them have shown anti-inflammatory,[6] antitumor,[7] antiarrhythmic,[8] and antidiabetic activities.[9] Besides alkaloids, there are limonoid-type triterpenes, such as obacunone and limonin in GHB,[10],[11],[12] and they exhibit significant antitumor,[13] antibacterial,[14] and antioxidation [15] activities. Nowadays, there are few reports on the pharmacokinetics investigation of alkaloids and limonoides of CGHB and SGHB, either few reports on the effect of the different absorptions of these active ingredients from crude and processed GHB. In this course of the research, a reliable, sensitive, and specific ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS) approach was established and verified for simultaneous quantitative analysis of six bioactive components in rat plasma. This method was successfully used to a pharmacokinetics study, in which it was found that oral administration of the saltwater processed product could affect the absorption of these bioactive compounds. Thein vivo pharmacokinetic study of the bioactive components of GHB could be necessary and helpful for further clinical applications and explanations of the processing mechanism.


   Materials and Methods Top


Herbal material and chemical reagents

GHB was purchased from Kangmei Pharmaceutical Co. Ltd. It was identified by Professor Bing Wang from Liaoning University of TCM. SGHB was produced in accordance with the Chinese Pharmacopeia (2015 ed). Simply, the CGHB were sealed in a container with the saltwater (100:2, GHB–salt, W/W), until the saltwater showed 100% infiltration (no residual solution in the container) into CGHB, then stir-fried in a wok at the temperature of 160°C for 5 min.

Standard substances (purity >98% by HPLC-UV) phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, obacunone, and nimodipine (Internal Standard [IS]) were purchased from Dalian Meilun Biotechnology company (Dalian, China). The acetonitrile, methanol (mass-grade), and formic acid (chromatographic-grade) were obtained from Merck (Darmstadt, Germany). Ultrapure water was prepared by a Milli-Q system (18.2 MΩ, Millipore, Billerica, USA). The other reagents and chemicals were of the highest grade analytical.

Preparation of aqueous extracts

An appropriate amount of CGHB was soaked with a ten-fold volume of distilled water for 30 min, after which it was decocted for 60 min and percolated. The residue was redissolved with an eight-fold volume of distilled water to decocted for 60 min and percolated again, then two filtrates were combined. The final concentration of CGHB aqueous extracts was 1 g/mL.[16] Respectively, the processed CGHB with saltwater aqueous extracts were prepared in the same method. All of the samples were maintained at 4°C before use.

Content determination of six major bioactive components in CGHB extract and SGHB extract

To determine the oral administration dose of GHB, the quantitation of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and obacunone in CGHB and SGHB extracts were carried out. The aqueous extracts of CGHB and SGHB were diluted ten times with methanol, and the diluted solution was centrifuged at 5000 rpm for 15 min. The supernatants were filtered through a 0.45-μm Millipore filter before HPLC analysis. A 10 μL sample was injected into the HPLC system with a Waters C18 column (4.6 mm × 150 mm 5 μm). To determine the content of alkaloids, the mobile phase was 0.025 mol/L KH2 PO4-acetonitrile (60:40) with the flow rate of 1.0 mL/min at 30°C, via setting the detective wavelength at 284 nm. For obacunone, the mobile phase was 0.01 mol/L H3 PO4-acetonitrile (55:45) with the flow rate of 1.0 mL/min at 30°C, via setting detective wavelength at 210 nm. The concentration of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and obacunone in CGHB extract were 0.18, 0.12, 4.31, 5.21, 9.26, and 0.16 mg/g, respectively, and 0.19, 0.13, 4.26, 5.22, 9.77, and 0.16 mg/g, respectively, in SGHB extract.

Ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry conditions

The analysis of pharmacokinetic was carried out by a Waters ACQUITY UPLC system and a Xevo TQ-S mass spectrometer. Moreover, the chromatographic separation was performed on a Waters UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) at 35°C. The composition of mobile phase was 0.1% formic acid water (A) and 0.1% formic acid acetonitrile (B). The gradient elution program was shown in [Table 1], and run at a flow rate of 0.3 mL/min. Each sample was placed in an autosampler at 4°C.
Table 1: Gradient elution program of mobile phase

Click here to view


Most of the bioactive compounds of GHB are alkaloids, and alkaloids have strong signal response in positive scan mode. Therefore, the positive ion mode was applied to detect the samples. To receive a richer mass spectral abundance of precursor and product ions, the MS condition was conducted as follows: source temperature 150°C; capillary 3000 V; cone voltages 50 V; desolvation gas (N2) flow 900 L/h; desolvation temperature 450°C; and cone gas flow 50 L/h. The majorization of collision energy was according to the chemical standards, and using helium for collision gas of collision-induced dissociation. Quantitative analysis was executed by the multiple reactions monitoring (MRM). The precursor → product ion transitions of m/z 342.17 → 192.15, m/z 342.18 → 265.16, m/z 338.15 → 323.03, m/z 352.15 → 336.20, m/z 336.07 → 320.29, m/z 455.23 → 161.14 and m/z 419.21 → 343.17 were employed for quantification of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, obacunone, and nimodipine. The results are shown in [Table 2] and [Figure 1].
Table 2: Optimized multiple reaction monitoring parameters for analytes and internal standard

Click here to view
Figure 1: The products spectra and fragmentation reaction of the seven compounds in positive electrospray ionization mode: (a) phellodendrine, (b) magnoflorine, (c) jatrorrhizine, (d) palmatine, (e) berberine, (f) obacunone, and (g) nimodipine

Click here to view


Preparation of standard solutions and quality control samples

The stock solutions of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, obacunone, and nimodipine (IS) at concentration of 74.80, 63.40, 63.20, 60.10, 61.20, 62.80, and 5.00 μg/mL were, respectively, prepared by dissolving the accurately weighed seven corresponding reference substances in methanol. A series of mixed standard stock solutions were obtained by diluting with methanol. The range of the concentrations of each standards were phellodendrine 0.37–119.76 ng/mL, magnoflorine 0.79–2028.80 ng/mL, jatrorrhizine 0.79–252.80 ng/mL, palmatine 0.75–240.4 ng/mL, berberine 1.53–489.60 ng/mL, and obacunone 0.79–121.60 ng/mL. The seven calibration solutions samples were prepared by the appropriate amount of the mixing standard stock solutions (100 μL), IS (20 μL) and blank plasma (100 μL). At last, the seven calibration solutions were obtained at the concentrations of 0.37, 3.74, 7.48, 14.96, 29.94, 59.88, and 119.76 ng/mL for phellodendrine; 0.79, 1.58, 15.85, 63.40, 253.60, 1014.40, and 2028.80 ng/mL for magnoflorine; 0.79, 1.58, 15.80, 31.60, 63.20, 126.40, and 252.8 ng/mL for jatrorrhizine; 0.75, 1.50, 15.00, 30.00, 60.00 120.00, and 240.00 ng/mL for palmatine; 1.53, 15.30, 30.60, 61.20, 122.40, 244.80, nd 489.60 ng/mL for berberine; and 0.79, 1.57, 3.14, 6.28, 31.4, 62.80, and 121.60 ng/mL for obacunone. Quality control (QC) samples were prepared at the concentrations of 0.8, 9, and 90 ng/mL for phellodendrine; 1.5, 40, and 1530 ng/mL for magnoflorine; 1.5, 20, and 200 ng/mL for jatrorrhizine; 4, 20, and 200 ng/mL for palmatine; 4, 40, and 360 ng/mL for berberine; and 2, 15 and 90 ng/mL for obacunone. All the samples were maintained at 4°C before use.

Preparation of plasma samples

About 20 μL of IS solution (5 μg/mL nimodipine) was added to 100 μL plasma samples by vortex-mixing for 30 s, then 400 μL of acetonitrile solution was spiked and vortexed for 180 s. After centrifugation (13,000 rpm, 10 min), the supernatant was diverted to another cuvette and dried with nitrogen gas at 37°C. A 100 μL of initial mobile phase was applied to redissolve the residue, then vortexed for 180 s, and centrifuged (13,000 rpm, 10 min). A 2 μL supernatant solution was used for pharmacokinetic analysis.

Animals

The Sprague–Dawley rats (weight: 200 ± 20 g, male) were purchased from Liaoning Changsheng Bio-Technology Co., Ltd. (Certification No.:SCXK [LN] 2010-0001), housed in the plastic cages at the temperature of 22°C–24°C, could drink and eat ad libitum. All the animals were kept for 7 days to adapt to the environment before the start of the experiment, and fasted for 12 h before dosing. The study protocol was authorized by the Animal Ethics Committee of Liaoning University of TCM.

Method validation

Selectivity

The selectivity of the assay was evaluated by comparing the chromatogram peaks of blank plasma and blank plasma added with phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, obacunone, and IS, along with plasma samples achieved after administration of GHB aqueous extract.

Linearity of calibration curves and lower limit of quantification

The calibration curve involved seven concentration levels and was established based on the peak area ratios (Y) of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and obacunone to the nimodipine (IS) versus the concentration standards (X) using the weighted least square linear regression (1/X 2). The LLOQ (Lower Limit of Quantification) of the method was evaluated as the lowest concentrations of the calibration curve which would be quantitative analysis by the value of an S/N ≥ 10 with precision and accuracy well applied.

Precision and accuracy

Six replicates of each concentration of QC sample were tested for the precision and accuracy validation. The intraday precision and accuracy were analyzed by the QC samples determined on the same day, and the interday precision and accuracy were measured by the QC samples on the 3 consecutive days. The precision was defined as relative standard deviation (RSD)%, and accuracy was expressed as relative error (RE)%, all of these values should be within ± 15%.

Extraction recovery and matrix effect

The extraction recoveries of the assay were calculated using each QC concentrations by comparing the peak areas from plasma samples with those achieved by the extracted blank plasma added with the corresponding analytes and IS. The matrix effect was determined by comparing the peak areas of the blank plasma which the postextracted matrix was supplemented with analytes and IS with those of the samples in the solution of water/acetonitrile (50:50).

Stability

The stability study was based on the quantitation of the low-, middle-, and high-QC concentration under different conditions: For 6 h at room temperature, at −80°C for 30 days, after three cycles of repeated freezing–thawing (from −80°C to –25°C) for 3 consecutive days and maintaining the extracted samples at 4°C for 24 h in the autosampler.

Pharmacokinetic study

The experimental rats were randomly divided into two groups: CGHB group and SGHB group. Then, the animals were orally treated with the CGHB and SGHB extracts at a single dose of 10.0 g/kg. The whole blood samples 0.25 mL in volume were achieved from orbital vein, after 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 h of the oral administration. All the blood samples were processed to centrifuge (3800 rpm, 10 min) to get plasma and then stored the samples at −80°C before analysis.

The verified approach was successfully used to a pharmacokinetic investigation for simultaneous quantitation of the five alkaloids and one triterpene in rat after administration of CGHB and SGHB. Data of sample information were obtained by MassLynx (Version 4.1) and processed by Drug and Statistics software (Version 3.0, Shanghai, China). The statistics of the results were calculated by the SPSS 19.0 software (IBM company, New York, USA). The mean concentration–time curves of each analyte from CGHB and SGHB were showed in [Figure 2]. The pharmacokinetic profile was analyzed by using a noncompartmental model.
Figure 2: Mean plasma concentration–time curve for (a) phellodendrine, (b) magnoflorine, (c) jatrorrhizine, (d) palmatine, (e) berberine, and (f) obacunone in rat plasma after oral administration of CGHB and SGHB

Click here to view



   Results and Discussion Top


Validation of the analytical method

Selectivity

Representative positive ion chromatograms of blank plasma, blank plasma added with the analytes and IS, along with plasma samples collected after oral administration of GHB for 1 h are illustrated in [Figure 3]. The figure demonstrated the good resolution chromatogram and without interference. Each retention time of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, obacunone, and IS were approximately 1.03, 1.10, 2.42, 3.69, 4.15, 6.61, and 7.05 min, respectively.{Figure 3}

Linearity of calibration curves and LLOQ

[Table 3] shows the linear regression analysis of phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and obacunone exhibited good linearity, with all of the correlation coefficients higher than 0.9906 over ranges of 0.37–119.76 ng/mL, 0.79–2028.80 ng/mL, 0.79–252.80 ng/mL, 0.75–240.00 ng/mL, 1.53–489.60 ng/mL, and 0.79–121.60 ng/mL, respectively. The values of the LLOQs were measured at a (S/N) ratio of ≥10, which were suitable for pharmacokinetic investigation.
Table 3: The regression equations, linear ranges, and lower limit of quantifications for the determination of the analytes in rat plasma

Click here to view


Precision and accuracy

The precision was demonstrated as RSD%, and the accuracy was demonstrated as RE% of the QC samples. The intra- and inter-day precision and accuracy were calculated by six replicates of the QC samples at low, medium, high concentration on the same day for 3 consecutive days. [Table 4] showed the precision and accuracy of the method were acceptable and satisfactory, indicating this method could quantify the analytes in rat reliably.
Table 4: Precision and accuracy for the analytes in rat plasma (n=6)

Click here to view


Extraction recovery and matrix effects

[Table 5] summarized that the extraction recoveries were ranged from 85.20%–96.27% for each analyte and 90.05% for IS. The results indicated this means was within the acceptance criteria. Meanwhile, the matrix effects of all the analytes at each QC level ranged from 87.72% to 107.25%, could be expressed no notable matrix effects.
Table 5: Matrix effects and extraction recovery for the analytes in rat plasma (n=6)

Click here to view


Stability

The stability test results were demonstrated in [Table 6]. It showed all the analytes were stable for 6 h at room temperature, for 30 days at −80°C, after repeated freeze-thaw cycles for 3 days and maintaining the extracted samples at 4°C for 24 h in the autosampler. The results indicated that the developed method is acceptable for pharmacokinetic investigation.
Table 6: Stability of each analyte in rat plasma under different storage conditions (n=6)

Click here to view


Application to pharmacokinetic study

We established a validated and successful method for simultaneous quantitation of five alkaloids and one triterpene in rat after oral administration of CGHB and SGHB. The mean concentration–time curves and pharmacokinetic profiles of each analyte from CGHB and SGHB were shown in [Figure 2] and [Table 7].
Table 7: Pharmacokinetic parameters of each analyte in rat plasma after oral administration of crude Phellodendri amurensis cortex and saltwater processed Phellodendri amurensis cortex (n=6)

Click here to view


In GHB, phellodendrine, magnoflorine, jatrorrhizine, palmatine, and berberine are alkaloids compounds. As shown in [Figure 2], most alkaloids compounds from GHB to reach the maximum concentration within 1 h of oral administration. At the same time, there was another small peak observed at almost 2 h of the alkaloids. The double-peak phenomenon of alkaloids was consistent with the literature and very likely owing to distribution, reabsorption, and enterohepatic circulation.[16],[17],[18] compared with alkaloid compounds, obacunone is a limonin-type triterpene ingredient from GHB, and there was only one peak in the concentration–time curve.

[Table 7] demonstrated that no remarkable difference between CGHB and SGHB in parameters of half-life (T½) and time for maximum of drug concentration except magnoflorine, suggesting that saltwater processing did not have influence the absorption rates of this compounds obviously. However, the mean maximum of drug concentration (Cmax) values of phellodendrine, magnoflorine, jatrorrhizine, palmatine, and berberine (74.838 ± 13.720, 762.045 ± 276.405, 6.587 ± 1.413, 34.123 ± 7.877 and 57.335 ± 14.474 ng/mL, respectively) from the SGHB group were 1.76-, 2.38-, 1.10-, 1.01-, and 1.83-fold higher than the values from the CGHB group. The AUC0-t values of phellodendrine, magnoflorine, jatrorrhizine, palmatine, and berberine (189.374 ± 31.909, 2114.721 ± 540.042, 23.685 ± 5.281, 153.032 ± 24.552, and 352.011 ± 50.696 h•ng/mL, respectively) were 1.15-, 1.40-, 1.49-, 1.22-, and 1.25-fold higher than the values of the CGHB group. On the contrary, the Cmax value of obacunone from SGHB is lower than those in the CGHB group, similar to the AUC0-t value. However, there is no remarkable difference between the two groups (P > 0.05). It can be inferred that the saltwater processing might mainly affect the absorption of alkaloids compounds and increase them other than the triterpene compounds from GHB.

The significant raises in Cmax value of alkaloid components from the SGHB group confirmed the saltwater processing could increase these compounds exposure in plasma. Moreover, the remarkable increase of the alkaloid compounds in the plasma from the SGHB group might have caused a substantial increase in clearing heat and removing toxicity activity of GHB. This result appeared to indicate the saltwater processing might have influence on the absorption of the active ingredient. In TCM, a high amount of Chinese Materia medicine should be processed with saltwater, and it is often reported that saltwater processing could enhance the absorption of bioactive compounds, such as those from Achyranthes bidentata,[19]Semen cuscutae,[20]Psoralea corylifolia L.,[21] and Anemarrhenae rhizoma.[22] This could indicate that the scientific nature of Chinese Materia medicine processing could increase the absorption of drugs through the corresponding processing methods, thereby enhancing efficacy. However, how Chinese Materia medicine processing specifically enhances absorption, e.g., increasing the permeability of endothelial cells, still requires further research.


   Conclusion Top


In summary, a simultaneous quantitative analysis method was established for the determination of five alkaloids and one triterpene from P. amurensis cortex in rat plasma. We evaluated the complete pharmacokinetic method and found the different pharmacokinetic profiles of these six components in plasma between the crude and saltwater processed GHB. It was shown that the pharmacokinetic behavior of the alkaloids compounds, including AUC0-t and Cmax, exhibited significant differences. In addition, the results indicated that the saltwater processing could increase the absorption of the alkaloids components, which might clarify the principle of bioactivity enhancement after processing from GHB.

Financial support and sponsorship

This work was supported by grants from the National Natural Science Foundation of China (No. 81274083) and Liaoning Province Natural Science Fund Guidance Plan (20180550942).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Chinese Pharmacopoeia Commission. Pharmacopeia of the People's Republic of China. 2015 edition. Beijing, China: China Medical Science Press; 2015.  Back to cited text no. 1
    
2.
Nanjing University of Chinese Medicine. Grand Dictionary of Chinese Materia Medica. Shanghai, China: Shanghai Science and Technology Press; 2006.  Back to cited text no. 2
    
3.
Jia ZT. Science of Processing Chinese Materia Medica. 2nd ed. Shanghai, China: Shanghai Science and Technology Press; 2008.  Back to cited text no. 3
    
4.
Wang T. Recording Summary on Traditional Chinese Medicine Processing Methods of All Ages. 1st ed. Nanchang, China: Jiangxi Science and Technology Press; 1998.  Back to cited text no. 4
    
5.
Zhu SL, Dou SS, Liu XR, Liu RH, Zhang WD, Huang HL, et al. Qualitative and quantitative analysis of alkaloids in cortex phellodendri by HPLC-ESI-MS/MS and HPLC-DAD. Chem Res Chin Univ 2011;27:38-44.  Back to cited text no. 5
    
6.
Xian YF, Mao QQ, Ip SP, Lin ZX, Che CT. Comparison on the anti-inflammatory effect of Cortex phellodendri Chinensis and Cortex Phellodendriamurensis in 12-O-tetradecanoyl-phorbol-13-acetate-induced ear edema in mice. J Ethnopharmacol 2011;137:1425-30.  Back to cited text no. 6
    
7.
Liu D, Meng X, Wu D, Qiu Z, Luo H. A natural isoquinoline alkaloid with antitumor activity: Studies of the biological activities of berberine. Front Pharmacol 2019;10:9.  Back to cited text no. 7
    
8.
Wang LH, Yu CH, Fu Y, Li Q, Sun YQ. Berberine elicits anti-arrhythmic effects via IK1/Kir2.1 in the rat type 2 diabetic myocardial infarction model. Phytother Res 2011;25:33-7.  Back to cited text no. 8
    
9.
Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of berberine. Med Sci Monit 2011;17:RA164-7.  Back to cited text no. 9
    
10.
Miyake M, Inaba N, Ayano S, Ozaki Y, Maeda H, Ifuku Y, et al. Limonoids in Phellodendron amurense (Kihada). Yakugaku Zasshi 1992;112:343-7.  Back to cited text no. 10
    
11.
Min YD, Kwon HC, Yang MC, Lee KH, Choi SU, Lee KR. Isolation of limonoids and alkaloids from Phellodendronamurense and their multidrug resistance (MDR) reversal activity. Arch Pharm Res 2007;30:58-63.  Back to cited text no. 11
    
12.
Zhang F, Shi J, Zhao JL, Tong LK, Jia TZ. Determination of limonin and obacunone in Phellodendri amurensis cortex, phellodendri Chinensis cortex and their processed products by HPLC. Chin Tradit Patient Med 2011;4:634-7.  Back to cited text no. 12
    
13.
Miller EG, Porter JL, Binnie WH, Guo IY, Hasegawa S. Further studies on the anticancer activity of citrus limonoids. J Agric Food Chem 2004;52:4908-12.  Back to cited text no. 13
    
14.
Kiplimo JJ, Koorbanally NA. Antibacterial activity of an epoxidised prenylated cinnamaldehdye derivative from Vepris glomerata. Phytochem Lett 2012;5:438-42.  Back to cited text no. 14
    
15.
Breksa AP 3rd, Manners GD. Evaluation of the antioxidant capacity of limonin, nomilin, and limonin glucoside. J Agric Food Chem 2006;54:3827-31.  Back to cited text no. 15
    
16.
Lei X, Shan G, Zhang F, Liu P, Meng L, Jia T. Determination and comparison of alkaloids and triterpenes among tissues after oral administration of crude and processed phellodendri Chinensis cortex by UPLC-qqQ-MS. Nat Prod Res 2019:1-4. doi: 10.1080/14786419.2018.1560293.  Back to cited text no. 16
    
17.
Liu L, Wang ZB, Song Y, Yang J, Wu LJ, Yang BY, et al. Simultaneous determination of eight alkaloids in rat plasma by UHPLC-MS/MS after oral administration of Coptisdeltoidea C. Y. Cheng et Hsiao and Coptis Chinensis Franch. Molecules 2016;21. pii: E913.  Back to cited text no. 17
    
18.
Sun L, Ding F, You G, Liu H, Wang M, Ren X, et al. Development and validation of an UPLC-MS/MS method for pharmacokinetic comparison of five alkaloids from jinqi Jiangtang tablets and its monarch drug coptidis rhizoma. Pharmaceutics 2017;10. pii: E4.  Back to cited text no. 18
    
19.
Tao Y, Du Y, Li W, Cai B. Development and validation of an UHPLC-MS/MS approach for simultaneous quantification of five bioactive saponins in rat plasma: Application to a comparative pharmacokinetic study of aqueous extracts of raw and salt-processed Achyranthesbidentata. J Pharm Biomed Anal 2018;151:164-9.  Back to cited text no. 19
    
20.
Yang S, Xu H, Zhao B, Li S, Li T, Xu X, et al. The difference of chemical components and biological activities of the crude products and the salt-processed product from Semen cuscutae. Evid Based Complement Alternat Med 2016;2016:8656740.  Back to cited text no. 20
    
21.
Gao Qq, Yan Cp, Xu Zs, Wu Y, Weng Zb, Zhao Gh, et al. Evaluation of the influence of salt processing on pharmacokinetics of psoralen and isopsoralen in Psoraleacorylifolia L. Biomed Chromatogr 2016;30:528-35.  Back to cited text no. 21
    
22.
Ji D, Su X, Huang Z, Wang Q, Lu T. A novel ultra high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of xanthones and steroidal saponins in crude and salt-processed Anemarrhenae rhizoma aqueous extracts. J Sep Sci 2018;41:2310-20.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
    Results and Disc...
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed36    
    Printed0    
    Emailed0    
    PDF Downloaded6    
    Comments [Add]    

Recommend this journal