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AIM To identify the optimal oral dosing time of Da-Cheng-Qi decoction(DCQD) in rats with acute pancreatitis(AP) based on the pharmacokinetic and pharmacodynamic parameters.METHODS First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4 h G(a), 12 h G(a) and 24 h G(a)]. The NG(a) and model groups were administered DCQD(10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4 h G(b), 12 h G(b) and 24 h G(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared.RESULTS The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12 h G(a) group were higher than those in the 4 h G(a) group in the pancreatic tissues(P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values(AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12 h G(a) group were larger than those in the 4 h G(a) or 24 h G(a) groups. The 12 h G(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12 h G(b) and 24 h G(b) groups were higher than in the MG(b)s(96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24 h G(b) group, the IL-10 level was higher than in the other two treatment groups(251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4 h G(b) and 12 h G(b) groups compared to theMG(b)s(89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05). CONCLUSION Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of antiinflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.
AIM To identify the optimal oral dosing time of Da-Cheng-Qi decoction (DCQD) in rats with acute pancreatitis (AP) based on the pharmacokinetic and pharmacodynamic parameters. METHODS First, 24 male Sprague-Dawley rats were divided into a sham-operated The NG (a) and model groups were administered DCQD (10 g / kg) and the three model groups [4 h G (a), 12 h G (a) and 24 h G .BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG (b)] and three treatment groups [4 h G (b), 12 h G (b) and 24 h G Three corresponding control groups [MG (b) s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared .RESULTS The concentrations of emodin, naringin , honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12 hG (a) group were higher than those in 4 hG (a) group in the pancreatic tissues (P <0.05) -time curve from time 0 to the time the last measurable concentration values (AUC0 → t) for rhein, chrysophanol, magnolol and naringin in the 12 h G (a) group were larger than those in 4 h G (a) or The 12 h G (a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12 h G (b) and 24 h G (b) groups were higher while in the MG (b) s (96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P <0.05) 0 leveThe IL-6 levels displayed a decrease in the 4 h G (b) and 12 h G (b). The IL-6 levels displayed a decrease in the 4 h G (b) and 12 h G (b ) groups compared to the MG (b) s (89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P <0.05). CONCLUSION Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of antiinflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.