Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis

doi:10.3748/wjg.v26.i22.3056

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Jun 14, 2020; 26(22): 3056-3075
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3056

Table 1 Pharmacokinetic parameters of the eight components of Dachengqi decoction in serum (n = 6)

Parameter	SOG₁	MG₁	MG₂	MG₃
Emodin
AUC 0-t	1605.0 ± 1029.5	359.3 ± 187.1^a	362.5 ± 67.4	427.5 ± 299.3
T 1/2z	5.2 ± 1.4	18.9 ± 12.5^a	9.0 ± 3.2	22.6 ± 9.0
T max	0.6 ± 0.3	3.5 ± 1.6^a	3.5 ± 1.6	0.3 ± 0^d^c
C max	620.733 ± 477.0	34.1 ± 22.5^a	29.8 ± 8.8	125.2 ± 90.9^d^c
Aloe-emodin
AUC 0-t	19206.1 ± 7275.8	11860.0 ± 4393.20	20181.9 ± 7660.2	37303.2 ± 13970.9^d
T 1/2z	7.0 ± 1.9	5.4 ± 2.1	6.4 ± 0.8	8.1 ± 5.4
T max	1.6 ± 1.6	1.4 ± 0.7	3 ± 1.2	0.7 ± 0.3^c
C max	3797.0 ± 727.7	2203.9 ± 1156.1	2398.4 ± 708.9	8349.5 ± 3969.4^d^c
Rhein
AUC 0-t	31571.7 ± 8961.8	13308.8 ± 8524.4^a	61966.5 ± 18335.3^b	38030.3 ± 22227.7^d^c
T 1/2z	4.1 ± 1.5	6.5 ± 2.3	4.8 ± 0.8	20.8 ± 10.0^d^c
T max	0.8 ± 0.2	6.5 ± 2.3^a	1.7 ± 0.7^b	1.6 ± 1.6^d
C max	11807.5 ± 2771.1	2204.3 ± 353.4^a	9245.7 ± 1284.0^b	11113.2 ± 5342.5^d
Chrysophanol
AUC 0-t	29977.3 ± 7570.0	15682.3 ± 5428.0^a	28337.7 ± 8880.5^b	26358.6 ± 4312.1^d
T 1/2z	5.7 ± 1.5	4.8 ± 1.0^a	4.7 ± 10.0	6.9 ± 4.5
T max	1.4 ± 0.7	3.3 ± 3.2^a	1.5 ± 0.6^b	1.8 ± 1.7
C max	7766.1 ± 2796.1	2018.9 ± 1227.5^a	4153.7 ± 2621.4	4318.1 ± 2458.9
Rheochrysidin
AUC 0-t	867.505 ± 867.5	3665.5 ± 1693.3^a	3032.0 ± 1011.6	1510.264 ± 727.3^d
T 1/2z	6.1 ± 1.0	4.3 ± 1.2	4.3 ± 1.6	9.4 ± 1.5^d^c
T max	1 ± 0.7	1.9 ± 1.5	2.2 ± 1.4	1.5 ± 0.6
C max	197.5 ± 64.0	728.8 ± 387.4^a	489.8 ± 176.2	172.9 ± 110.7^d
Naringin
AUC 0-t	353.0 ± 261.0	6296.0 ± 1271.2^a	5449.1 ± 2183.0	2188.5 ± 752.5^d^c
T 1/2z	6.4 ± 0.8	4.1 ± 0.7^a	5.4 ± 1.3	5.8 ± 5.8
T max	0.8 ± 0.2	1.8 ± 1.7	2.3 ± 1.3	2.5 ± 1
C max	125.6 ± 121.0	806.2 ± 730.9^a	682.4 ± 380.4	257.6 ± 26.4^d
Naringenin
AUC 0-t	3064.2 ± 829.9	6344.8 ± 1199.2^a	3051.6 ± 932.6^b	3926.0 ± 1014.2^d
T 1/2z	7.368 ± 1.5	4.5 ± 1.7	10.9 ± 3.4^b	7.8 ± 1.4
T max	0.9 ± 0.7	2.3 ± 1.0	1.6 ± 1.6	0.6 ± 0.1^d
C max	634.2 ± 228.6	805.3 ± 113.8	488.9 ± 316.7	581.1 ± 161.7
Magnolol
AUC 0-t	143.8 ± 35.0	34.8 ± 8.0^a	69.4 ± 14.8	64.2 ± 10.8
T 1/2z	9.0 ± 6.2	10.6 ± 1.4	13.9 ± 2.5	24.5 ± 9.1^d
T max	0.7 ± 0.3	0.8 ± 0.8	3.5 ± 1^b	0.5 ± 0.3^c
C max	30.6 ± 19.8	5.3 ± 1.7^a	5.5 ± 0.9	12.8 ± 3.1

Rats were randomly divided into SOG₁ and three model groups (MG_1, MG_2, and MG₃), and orally dosed with Dachengqi decoction (DCQD) (10 g/kg). Blood samples were collected via the tail vein at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h after a single dose of DCQD to detect its main components. The pharmacokinetic parameters were calculated with pharmacokinetic statistic software DAS2.0.1. SOG₁: Sham-operated group with the dosing time at 4 h after operation; MG₁, MG₂, and MG₃: Rats were dosed orally with DCQD at 4 h, 12 h, and 24 h after acute pancreatitis induction, respectively. Data are presented as the mean ± SD (n = 6). MG₁ vs SOG₁.

^aP < 0.05; MG₂ vs MG₁.

^bP < 0.05; MG₃ vs MG₂.

^cP < 0.05; MG₃ vs MG₁.

^dP < 0.05. DCQD: Dachengqi decoction.

Table 2 Concentrations of the ten major components of Dachengqi decoction in tissue samples (n = 6)

Parameter	SOG₁	MG₁	MG₂	MG₃
Heart
Emodin	3.21 ± 0.13	1.25 ± 0.09^a^d	2.24 ± 0.14^c	2.45 ± 0.21
Aloe-emodin	56.72 ± 5.67	21.96 ±7.21^a^d	28.45 ± 8.47	31.53 ± 1.34
Rhein	0	0	0	0
Chrysophanol	15.57 ± 4.63	6.43 ± 1.2^a	5.65 ± 2.4	7.59 ± 1.98
Rheochrysidin	1.93 ± 0.89	0	0	2.41 ± 3.67
Naringin	40.36 ± 1.38	0.85 ± 0.02^a^d	9.62 ± 0.37^c	10.49 ± 0.21
Naringenin	420.68 ± 67.81	160.09 ± 12.61^a	924.79 ± 34.67^c	270.25 ± 48.51
Hesperidin	12.22 ± 0.94	5.05 ± 1.2^a	10.33 ± 4.3 ^c	5.24 ± 1.98
Magnolol	0.21 ± 0.04	0.18 ± 0.02	0.02 ± 0.01 ^c	0.21 ± 0.10
Honokiol	0.59 ± 0.07	0.24 ± 0.04^a^d	0.9 0 ± 0.07 ^c	0.73 ± 0.09
Liver
Emodin	14.24 ± 6.21	7.27 ± 2.37^a	3.97 ± 1.67 ^c	8.36 ± 4.23
Aloe-emodin	506.09 ± 32.78	438.4 ± 123.47	122.87 ± 79.23 ^c	383.40 ± 101.31
Rhein	45.58 ± 63.23	0	0	0
Chrysophanol	132.65 ± 7.43	40.38 ± 20.81^a^d	17.10 ± 3.24 ^c	18.47 ± 0.8
Rheochrysidin	20.27 ± 0.98	1.42 ± 0.14^a^d	3.39 ± 0.29 ^c	0.18 ± 0.23
Naringin	148.20 ± 8.94	13.19 ± 10.23^a	27.07 ± 9.81	23.49 ± 8.67
Naringenin	1707.40 ± 99.46	1459.04 ± 98.67^a^d	692.88 ± 102.43^c	1855.76 ± 79.23
Hesperidin	60.03 ± 18.87	6.53 ± 1.23^a^d	2.27 ± 0.94^c	13.65 ± 0.23
Magnolol	2.88 ± 0.41	3.34 ± 1.64	1.62 ± 0.72 ^c	2.42 ± 0.23
Honokiol	3.00 ± 0.78	2.02 ± 0.78	1.64 ± 0.24	3.03 ± 0.31
Lung
Emodin	3.87 ± 1.43	2.08 ± 0.98	2.99 ± 0.43	3.1 ± 1.02
Aloe-emodin	66.98 ± 33.62	56.88 ± 20.45^d	34.94 ± 13.67 ^c	88.12 ± 23.21
Rhein	143.74 ± 73.64	164.27 ± 64.81	72.59 ± 42.31 ^c	171.52 ± 57.84
Chrysophanol	19.05 ± 6.39	13.51 ± 9.43	15.1 ± 3.57	16.42 ± 4.81
Rheochrysidin	1.06 ± 0.17	0.18 ± 0.23^a	0.42 ± 0.02^c	0.23 ± 0.01
Naringin	12.55 ± 1.67	6.00 ± 3.2^a^d	8.37 ± 2.37^c	24.46 ± 4.17
Naringenin	422.09 ± 203.92	601.12 ± 176.64	567.53 ± 123.67	427.36 ± 204.81
Hesperidin	58.67 ± 15.81	22.74 ± 10.13^a^d	33.74 ± 10.32^c	77.35 ± 34.61
Magnolol	0.34 ± 0.19	0.35 ± 0.23	0.35 ± 0.04	0.46 ± 0.17
Honokiol	1.43 ± 0.19	1.42 ± 0.16^a	0.95 ± 0.02 ^c	0.82 ± 0.04
Kidney
Emodin	21.15 ± 10.28	27.75 ± 14.21	11.98 ± 5.67 ^c	26.31 ± 13.42
Aloe-emodin	1328.18 ± 159.73	279.04 ± 100.04^a^d	133.62 ± 92.43^c	720.74 ± 143.67
Rhein	154.59 ± 12.34	2.49 ± 0.98^a^d	37.72 ± 1.34^c	101.55 ± 2.78
Chrysophanol	108.89 ± 7.64	101.18 ± 7.84^a^d	46.84 ± 6.23^c	124.76 ± 4.32
Rheochrysidin	16.25 ± 2.79	15.23 ± 3.54	6.13 ± 0.98^c	13.57 ± 1.43
Naringin	208.08 ± 8.94	18.44 ± 3.64^a^d	0.94 ± 0.17^c	59.9 ± 7.63
Naringenin	2144.99 ± 147.81	2506.95 ± 100.07^a^d	2360.21 ± 143.64^c	1939.2 ± 127.68
Hesperidin	48.87 ± 4.81	9.13 ± 1.67^a	8.67 ± 1.32	9.90 ± 0.89
Magnolol	0.81 ± 0.2	0.52 ± 0.12^a^d	0.30 ± 0.03 ^c	1.14 ± 0.14
Honokiol	2.76 ± 0.31	1.56 ± 0.44^a^d	1.35 ± 0.23^c	2.63 ± 0.67
Intestine
Emodin	94.43 ± 37.23	19.73 ± 6.72^a^d	88.3 ± 24.23	122.66 ± 72.61
Aloe-emodin	4515.56 ± 342.67	1447.33 ± 109.73^a^d	975.33 ± 152.62^c	2202.32 ± 143.76
Rhein	214.49 ± 56.72	830.8 ± 48.63^a^d	130.67 ± 65.67	209.09 ± 100.3
Chrysophanol	714.88 ± 300.68	290.97 ± 110.37^a^d	410.67 ± 203.3^c	736.46 ± 45.67
Rheochrysidin	161.78 ± 80.93	37.9 ± 2.34^a^d	27.59 ± 17.61^c	191.14 ± 59.67
Naringin	2771.61 ± 67.81	604.19 ± 134.6^a^d	678.67 ± 57.63^c	1442.36 ± 100.75
Naringenin	1804.34 ± 307.16	1365.3 ± 153.62^a^d	1077.59 ± 174.63 ^c	3695.62 ± 483.54
Hesperidin	1156.54 ± 154.63	241.58 ± 72.61^a^d	265.59 ± 100.32 ^c	581.04 ± 201.63
Magnolol	17.13 ± 7.34	18.78 ± 6.43^d	18.15 ± 7.81^c	35.5 ± 5.67
Honokiol	18.7 ± 2.71	24.27 ± 2.43^a^d	17.14 ± 3.1^c	45.48 ± 4.58

Rats were randomly divided into SOG₁ and three model groups (MG_1, MG_2, and MG₃), and orally dosed with Dachengqi decoction (DCQD) (10 g/kg). Tissue samples were collected 24 h after a single dose to detect its main components. SOG₁: Sham-operated group with the dosing time at 4 h after operation; MG₁, MG₂, and MG₃: Rats were dosed orally with DCQD at 4 h, 12 h, and 24 h after AP induction, respectively. Data are presented as the mean ± SD (n = 6). MG₁ vs SOG₁.

^aP < 0.05; MG₂ vs MG₁. ^bP < 0.05; MG₃ vs MG₂.

^cP < 0.05; MG₃ vs MG₁.

^dP < 0.05.

Citation: Yao JQ, Zhu L, Miao YF, Zhu L, Chen H, Yuan L, Hu J, Yi XL, Wu QT, Yang XJ, Wan MH, Tang WF. Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis. World J Gastroenterol 2020; 26(22): 3056-3075
URL: https://www.wjgnet.com/1007-9327/full/v26/i22/3056.htm
DOI: https://dx.doi.org/10.3748/wjg.v26.i22.3056