博落回提取物对草鱼生长性能的影响及其效用成分的药代动力学和残留消除研究

doi:10.11843/j.issn.0366-6964.2025.08.039

Abstract

Abstract:

The objective of this study was to observe the growth-promoting effect of Macleaya cordata extract (MCE) on grass carp (Ctenopharyngodon idellus) and to characterize the pharmacokinetic properties and muscle residues of its main active components, sanguinarine (SAN) and chelerythrine (CHE). Four hundred and fifty grass carp weighing 10.5 g were randomly divided into 5 groups and fed with diets containing 0, 30, 60 and 120 mg·kg^-1 MCE Pulvis (MCEP) and betaine hydrochloride respectively for 60 days. A total of 120 grass carp weighing 250 g were randomly divided into 5 groups. MCE was administered intravenously (0.001 2 mg·kg^-1, 0.012 mg·kg^-1, 0.024 mg·kg^-1) or gavage (0.06 mg·kg^-1, 0.6 mg·kg^-1). The concentrations of SAN and CHE in blood were determined by liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS). Another 150 grass carp of 50 g were fed with MCEP (60 mg·kg^-1 feed) for 60 days. SAN and CHE contents in skinned muscle of grass carp were determined by LC-QQQ-MS. The results showed that MCE could significantly improve growth performance and condition factor of grass carp (PP < 0.05); After oral administration of 0.6 mg·kg^-1 MCE, the main pharmacokinetic (PK) parameters of MCE, SAN and CHE administered orally at 0.6 mg·kg^-1 were C_max=19.157±1.924 and 6.388±1.356 μg·L^-1, AUC_(0-t)=3.317±0.274 and 0.651±0.114 (μg·L^-1)·h, T_1/2=9.065±2.286 h (CHE had no valid data), respectively. 5 min after intravenous injection of 0.0245 mg·kg^-1 MCE, AUC_(0-t) of SAN and CHE were 37.132±4.124 and 0.614±0.039 (μg·L^-1) ·h, AUC_(0-∞) were 60.583±7.512 and 0.750±0.055 (μg·L^-1)·h, respectively; In the residue assay, SAN and CHE in muscle decreased below the limit of quantification on day 5 after withdrawal. The results suggested that 60 mg·kg^-1 MCEP could significantly improve the growth performance of grass carp. SAN and CHE in plasma showed PK characteristics of fast absorption, wide distribution and rapid elimination. However, at high doses, the two active substances exhibit significant nonlinear PK profiles; SAN and CHE in muscle were almost completely eliminated after 5 days withdrawal of MCE. This study is of great significance in the rational use of MCE, its development and related risk assessment.

Key words: Macleaya cordata extract, grass carp, growth properties, sanguinarine, chelerythrine, pharmacokinetics, residue elimination

CLC Number:

ZHANG Haoyang, LIU WEI, SUN Wenqing, XU Yufeng, LIU Zhiqin, YANG Zihui, DONG Zhen, ZENG Jianguo. Effects of Macleaya Cordata Extract on Growth Performance of Grass Carp and Pharmacokinetics and Residue Elimination of Its Utility Components[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(8): 4018-4030.

Figures/Tables 12

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References 35

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分析物 Analyte	保留时间/min Retention time	监测离子对(m/z) Monitoring ion pairs	碎裂电压/V Fragmentor voltage	碰撞能量/eV Collision energy
SAN	1.822	332.1→273.9^*，332.1→316.9	143	35
CHE	1.918	348.1→332.0^*，348.1→304.1	150	30
TET	1.756	356.0→192.0^*，356.0→165.0	142	26

组别 Groups	初始体重/g Initial body weight	终末体重/g Terminal body weight	相对增重率/% Relative weight gain rate	平均日增重/g Average daily gain	饵料系数 Feed coefficient
空白对照组 Blank control group	10.3±0.4^a	23.3±4.3^a	127.0±45.5^a	0.22±0.07^a	2.58±1.09^b
甜菜碱组 Betaine group	10.7±0.5^a	27.6±2.7^a	157.3±14.5^a	0.28±0.04^a	1.80±0.25^ab
30 mg·kg^-1 MCEP	10.4±0.6^a	24.1±3.2^a	131.1±16.8^a	0.23±0.04^a	2.25±0.39^ab
60 mg·kg^-1 MCEP	10.7±0.7^a	37.1±12.3^b	242.7±96.2^b	0.44±0.19^b	1.34±0.63^a
120 mg·kg^-1 MCEP	10.3±0.5^a	24.3±1.6^a	135.1±9.9^a	0.23±0.02^a	2.16±0.19^ab

组别 Groups	体长/cm Body length	体重/g Body weight	肝脏重/g Liver weight	肝体比 Hepatosomatic index	肥满度 Fulton′s condition index (K)
空白对照组 Blank control group	11.3±1.3	23.3±4.3	0.50±0.08	2.16±0.06^a	1.65±0.24^a
甜菜碱组 Betaine group	12.4±0.8	27.6±2.7	0.50±0.08	1.82±0.29^a	1.46±0.14^a
30 mg·kg^-1 MCEP	11.6±1.0	24.1±3.2	0.50±0.00	2.11±0.27^a	1.54±0.19^a
60 mg·kg^-1 MCEP	12.6±1.4	37.1±12.3	0.67±0.05	1.99±0.73^b	1.79±0.18^b
120 mg·kg^-1 MCEP	11.8±0.4	24.3±1.6	0.53±0.05	2.16±0.14^a	1.47±0.08^a

样品 Sample	分析物 Analyte	回归方程 Regression equation	相关系数 R²	线性范围 Linearity range
血浆 Plasma	SAN	y=0.002 104*x+0.007 727	0.999 8	0.5~200.0 μg·L^-1
血浆 Plasma	CHE	y=0.013 691*x+0.040 129	0.999 6	0.5~200.0 μg·L^-1
肌肉 Muscle	SAN	y=0.007 480*x+0.001 696	0.999 9	5.0~1 000.0 μg·kg^-1
肌肉 Muscle	CHE	y=0.059 915*x-0.014 136	0.999 9	5.0~1 000.0 μg·kg^-1

样品 Sample	分析物 Analyte	理论浓度/(μg·L^-1) Theoretical concentration	平均基质效应/% Mean matrix effect	基质效应RSD/% RSD of matrix effect
血浆 Plasma	SAN	0.500	100.493	1.407
		5.000	99.542	0.662
		50.000	99.047	0.750
	CHE	0.500	100.408	1.157
		5.000	96.982	0.752
		50.000	103.065	1.060
肌肉 Muscle	SAN	0.500	100.332	0.422
		5.000	99.635	0.272
		50.000	99.502	0.389
	CHE	0.500	100.376	0.651
		5.000	99.820	0.577
		50.000	100.242	0.675

Effects of Macleaya Cordata Extract on Growth Performance of Grass Carp and Pharmacokinetics and Residue Elimination of Its Utility Components

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基质 Matrix	分析物 Analyte	浓度/(μg·L^-1) Concentration	回收率/% Recovery rate	批内精密度/% Intra-batch precision	批间精密度/% Inter-batch precision
血浆 Plasma	SAN	0.500	98.895	5.273	5.552
		5.000	99.869	5.178	3.400
		50.000	98.119	3.129	2.338
	CHE	0.500	98.002	4.522	2.691
		5.000	99.350	0.816	2.094
		50.000	94.204	3.440	2.712
肌肉 Muscle	SAN	0.500	99.309	0.495	0.478
		5.000	98.941	0.408	0.413
		50.000	97.862	0.505	0.519
	CHE	0.500	100.587	0.516	0.576
		5.000	96.201	0.474	0.473
		50.000	97.656	0.525	0.501

样品 Sample	分析物 Analyte	QC理论浓度/(μg·L^-1) QC theoretical concentration	进样器稳定性 Stability at injector		长期稳定性 Long-term stability		室温稳定性 Room temperature stability		冻融稳定性 Freeze-thaw stability
样品 Sample	分析物 Analyte	QC理论浓度/(μg·L^-1) QC theoretical concentration	实测浓度/(μg·L^-1) Measured concentration	RSD/%	实测浓度/(μg·L^-1) Measured concentration	RSD/%	实测浓度/(μg·L^-1) Measured concentration	RSD/%	实测浓度/(μg·L^-1) Measured concentration	RSD/%
血浆 Plasma	SAN	0.500	0.845	3.226	0.566	2.387	0.548	2.239	0.552	5.113
		5.000	5.742	4.210	5.122	1.103	5.186	2.405	5.519	3.196
		50.000	58.729	1.629	50.542	0.571	53.678	3.871	52.836	1.926
	CHE	0.500	0.803	7.880	0.570	2.761	0.563	3.476	0.549	3.678
		5.000	5.252	3.922	5.130	1.732	5.225	2.952	5.557	4.380
		50.000	58.139	2.829	50.420	0.390	54.155	2.043	52.408	1.692
肌肉 Muscle	SAN	0.500	0.568	0.237	0.554	0.823	0.564	0.550	0.565	0.590
		5.000	5.641	0.375	5.564	0.333	5.642	0.451	5.631	0.461
		50.000	56.425	0.612	55.622	0.530	56.556	0.430	56.253	0.382
	CHE	0.500	0.565	0.730	0.557	0.533	0.568	0.315	0.564	0.341
		5.000	5.653	0.260	5.547	0.552	5.647	0.481	5.649	0.503
		50.000	56.375	0.456	55.466	0.610	56.468	0.629	56.529	0.551

化合物 Compounds	参数 Parameters	单位 Units	IH	OL	OH
SAN	C_max	μg·L^-1	-	19.157±1.924	41.161±2.988
	T_max	h	-	0.083±0.000	0.083±0.000
	AUC_(0-t)	(μg·L^-1) ·h	37.132±4.124	3.317±0.274	21.037±0.708
	AUC_(0-∞)	(μg·L^-1) ·h	60.583±7.512	-	29.596±2.749
	MRT_(0-t)	h	17.364±1.428	0.143±0.004	3.157±0.049
	T_1/2	h	27.330±6.637	-	9.065±2.286
	CL	L·h^-1·kg^-1	0.380±0.074	-	20.433±1.944
	V_d	L·kg^-1	18.464±3.317	-	261.945±47.457
CHE	C_max	μg·L^-1	-	6.388±1.356	16.130±1.874
	T_max	h	-	0.083±0.000	0.083±0.000
	AUC_(0-t)	(μg·L^-1) ·h	0.614±0.039	0.651±0.114	2.415±0.160
	AUC_(0-∞)	(μg·L^-1) ·h	0.750±0.055	-	-
	MRT_(0-t)	h	0.177±0.004	0.099±0.005	0.137±0.005
	T_1/2	h	0.180±0.010	-	-
	CL	L·h^-1·kg^-1	32.163±2.441	-	-
	V_d	L·kg^-1	9.065±0.573	-	-

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