Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca²⁺Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis

Abstract

Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.

Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction

“…e Chinese medicinal herbs in CQCQD were purchased from the West China Hospital of Sichuan University (Chengdu, China). e detailed composition and preparation procedures were described in our previous work [21]. L-ornithine and carbachol were freshly prepared before each experiment using normal saline as the dissolving solvent.…”

“…Intragastric administration of chaiqin chengqi decoction (CQCQD), a Chinese herbal formula that is widely used to treat patients with severe AP, decreased pancreatic and gut injury and improved gut motility parameters (serum VIP, iFABP, and substance P). is protective effect was partially via its regulating role of protein kinase C (PKC)-mediated Ca 2+ release in colonic smooth muscle cells (SMCs) [21]. Since L-arginine at high doses directly induces gut injury and dysmotility by releasing neurotransmitters [21], the effect of CQCQD on improving gut motility needs to be validated in other models of AP induced by toxins that have no direct effect on the gut.…”

“…is protective effect was partially via its regulating role of protein kinase C (PKC)-mediated Ca 2+ release in colonic smooth muscle cells (SMCs) [21]. Since L-arginine at high doses directly induces gut injury and dysmotility by releasing neurotransmitters [21], the effect of CQCQD on improving gut motility needs to be validated in other models of AP induced by toxins that have no direct effect on the gut. Furthermore, emerging evidence has shown that small intestine injury appeared early than colonic injury [12,14,22] and was the primary bacterial translation site [23].…”

Cognitive impairments induced by severe acute pancreatitis are attenuated by berberine treatment in rats

“…Berberine attenuates the severity of SAP and improves survival in SAP rats. It has been reported that repeated injections with high doses of L-arginine may induce AP in rodents with well-defined, gradually progressive pancreatic necrosis (14). In the present study, L-arginine was used to induce SAP, and disease severity was assessed by investigating alterations in pancreatic histopathology and serum amylase levels.…”

“…Rats were randomly divided into four groups (n=32 per group): Sham group, Sham + berberine group, SAP group and SAP + berberine group. The SAP model was induced via two intraperitoneal injections of 3 g/kg L-arginine (dissolved in normal saline, 1:5, w/v; Sigma-Aldrich; Merck KGaA, Darmstadt, Germany) at an interval of 1 h (14), whereas rats in the sham groups received equivalent volumes of a saline vehicle. Following the second injection of L-arginine, 100 mg/kg berberine (15) (dissolved in 1 ml normal saline/200 g body weight; Sigma-Aldrich; Merck KGaA) was administered immediately and then once a day for 6 consecutive days.…”