Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy.

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats.

Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries via inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP.

Zengye Decoction Attenuated Severe Acute Pancreatitis Complicated with Acute Kidney Injury by Modulating the Gut Microbiome and Serum Amino Acid Metabolome.

Objective: To explore the effect and underlying mechanism of Zengye decoction (ZYD), a traditional formula from China, on the severe acute pancreatitis (SAP) rat model with acute kidney injury (AKI). Methods: The SAP-AKI model was induced by 3.5% sodium taurocholate. Rats were treated with normal saline or ZYD twice and sacrificed at 36 h after modeling. Amylase, lipase, creatinine, blood urea nitrogen, kidney injury molecule 1(KIM-1), and multiple organs' pathological examinations were used to assess the protective effect of ZYD. Gut microbiome detected by 16S rRNA sequencing analysis and serum amino acid metabolome analyzed by liquid chromatography-mass spectrometry explained the underlying mechanism. The Spearman correlation analysis presented the relationship between microflora and metabolites. Results: ZYD significantly decreased KIM-1(P < 0.05) and the pathological score of the pancreas (P < 0.05), colon (P < 0.05), and kidney (P < 0.05). Meanwhile, ZYD shifted the overall gut microbial structure (ß-diversity, ANOSIM R = 0.14, P=0.025) and altered the microbial compositions. Notably, ZYD reduced the potentially pathogenic bacteria-Bacteroidetes, Clostridiales vadin BB60 group, and uncultured_Clostridiales_bacterium, but promoted the short-chain fatty acid (SCFA) producers-Erysipelotrichaceae, Bifidobacterium, Lactobacillus, and Moryella (all P < 0.05). Moreover, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) presented a remarkable change in amino acid metabolome after SAP-AKI induction and an apparent regulation by ZYD treatment (R2Y 0.878, P=0.01; Q2 0.531, P=0.01). Spearman's correlation analysis suggested that gut bacteria likely influenced serum metabolites levels (absolute r > 0.4 and FDR P < 0.02). Conclusions: ZYD attenuated SAP-AKI by modulating the gut microbiome and serum amino acid metabolome, which may be a promising adjuvant treatment.

Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury.

BACKGROUND: The complications acute lung injury and acute kidney injury caused by severe inflammation are the main reasons of high mortality of severe acute pancreatitis (SAP). These two complications can both lead to water metabolism and acid-base balance disorders, which could act as additional critical factors affecting the disease trend. Aquaporins (AQPs), which can regulate the transmembrane water transport, have been proved to participate in the pathophysiological process of SAP and the associated complications, such as acute lung injury and acute kidney injury. Thus, exploring herbs that can effectively regulate the expression of AQP in SAP could benefit the prognosis of this disease. AIM: To determine whether Yue-Bi-Tang (YBT) can regulate the water metabolism in rats with severe acute pancreatitis via regulating the expression of aquaporins. METHODS: Sprague-Dawley rats were randomly divided into three groups, sham operation group (SOG), model group (MG), and treatment group (TG). SAP was induced with 3.5% sodium taurocholate in the MG and TG. Rats in the TG were administered with YBT while SOG and MG rats were given the same volume of saline. Blood and tissue samples were harvested to detect serum inflammatory cytokines, histopathological changes, malondialdehyde and superoxide dismutase in the lung, and protein and mRNA expression of kidney injury molecule-1, α-smooth muscle actin, and vimentin in the kidney, and AQP1 and 4 in the lung, pancreas, and kidney. RESULTS: The serum interleukin-10, tumor necrosis factor α, and creatinine levels were higher in the MG than in the SOG. Tumor necrosis factor α level in the TG was lower than that in the MG. Malondialdehyde level in lung tissues was higher than in the SOG. The pathological scores and edema scores of the pancreas, lung, and kidney tissues in the MG were all higher than those in the SOG and TG. The protein expression of AQP4 in lung tissues and AQP1 in kidney tissues in the MG were higher than those in the SOG and TG. The expression of vimentin was significantly higher in the MG than in the SOG. The expression of AQP1 mRNA in the lung and kidney, and AQP4 mRNA in the kidney was up-regulated in the MG compared to the SOG. CONCLUSION: YBT might regulate water metabolism to reduce lung and kidney edema of SAP rats via decreasing AQP expression, and alleviate the tissue inflammatory injury.

Effect of Sheng-Jiang Powder on Gut Microbiota in High-Fat Diet-Induced NAFLD.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by next decade. Gut microbiota have been revealed playing an important role in the pathogenesis of NAFLD. Sheng-Jiang Powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great hepatoprotective properties, but the impact on gut microbiota has never been identified. Therefore, we performed this study to investigate the effect of SJP on gut microbiota in NAFLD mice. METHODS: NAFLD was induced by 12 weeks' high-fat diet (HFD) feeding. Mice were treated with SJP/normal saline daily for 6 weeks. Blood samples were obtained for serum biochemical indices and inflammatory cytokines measurement. Liver tissues were obtained for pathological evaluation and oil red O staining. The expression of lipid metabolism-related genes was quantified by RT-PCR and Western blotting. Changes in gut microbiota composition were analyzed by the 16s rDNA sequencing technique. RESULTS: HFD feeding induced significant increase in bodyweight and serum levels of TG, TC, ALT, and AST. The pathological examination revealed obvious hepatic steatosis in HFD feeding mice. Coadministration of SJP effectively protected against bodyweight increase and lipid accumulation in blood and liver. Increased expression of PPARγ mRNA was observed in HFD feeding mice, but a steady elevation of PPARγ protein level was only found in SJP-treated mice. Meanwhile, the expression of FASN was much higher in HFD feeding mice. Microbiome analysis revealed obvious changes in gut microbiota composition among diverse groups. SJP treatment modulated the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, including norank-f-Erysipelotrichaceae and Roseburia. CONCLUSIONS: SJP is efficient in attenuating HFD-induced NAFLD, and it might be partly attributed to the regulation of gut microbiota.

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

BACKGROUND: Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear. AIM: To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats. METHODS: This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated. RESULTS: For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration. CONCLUSION: Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.

Effect of Different-Volume Fluid Resuscitation on Organ Functions in Severe Acute Pancreatitis and Therapeutic Effect of Poria cocos.

OBJECTIVE: To explore the effect of different-volume fluid resuscitation (FR) on organ functions in severe acute pancreatitis (SAP) and to elucidate the therapeutic effect and mechanism of Poria cocos on organ injuries caused by high-volume FR. METHODS: 1. Clinical study: retrospective analysis of thirty-one patients about the effect of titrated fluid resuscitation protocol (TFR) on the occurrence of acute kidney injury (AKI) secondary to SAP. 2. Experimental study: rats (N = 30) were randomly divided into five groups: sham, model, low-volume FR (1.5 ml/kg/h), high-volume FR (10 ml/kg/h), and Poria cocos combined with high-volume FR (10 ml/kg/h + intraintestinal administration Poria cocos 5 g/kg); serum or plasma indicators and histopathologic scores were compared to explore the effect and mechanism of different fluid volumes and Poria cocos on organ function in SAP. RESULTS: The occurrence of AKI, fluid volume, and fluid velocity in TFR group was lower than that in the control group. Logistic regression analysis showed that increased Marshall scores and fluid velocity were risk factors for predicting occurrence of AKI in SAP. Low-volume FR decreased the levels of blood urea nitrogen (BUN), serum creatinine (Cr), matrix metalloproteinase (MMP), and pathologic scores of the pancreas and kidney. High-volume FR increased ascites, MMPs, and kidney pathologic scores. Poria cocos decreased the levels of BUN, Cr, MMPs, and pathologic scores of the pancreas and kidney and increased the arterial oxygen saturation. CONCLUSION: TFR-associated lower fluid volume and velocity reduced the occurrence of AKI secondary to SAP. High volume might aggravate AKI via increased MMP release leading to endothelial glycocalyx damage and vascular endothelial dysfunction. Poria cocos reduced MMP release, relieved glycocalyx damage, and alleviated the pancreas and kidney injury aggravated by high fluid volume in SAP. Therefore, endothelial glycocalyx protection might be a new strategy in the treatment of SAP.

Effect of Sheng-jiang powder on multiple-organ inflammatory injury in acute pancreatitis in rats fed a high-fat diet.

BACKGROUND: Obesity worsens inflammatory organ injury in acute pancreatitis (AP), but there is no effective preventive strategy. Sheng-jiang powder (SJP) has been shown to alleviate multiple-organ inflammatory injury in rats with high-fat diet-induced obesity. Hence, SJP is supposed to have an effect on multiple-organ inflammatory injury in AP in rats fed a high-fat diet. AIM: To explore how obesity may contribute to aggravating inflammatory organ injury in AP in rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet. METHODS: Rats were randomly assigned to a control group (CG), an obese group (OG), and an SJP treatment group (SG), with eight rats per group. The rats in the OG and SG were fed a high-fat diet. From the third week, the rats in the SG were given oral doses of SJP (5 g/kg of body weight). After 12 wk, AP was induced in the three groups. Serum amylase level, body weight, Lee's index, serum biochemistry parameters, and serum inflammatory cytokine and tissue cytokine levels were assessed, and the tissue histopathological scores were evaluated and compared. RESULTS: Compared with the CG, serum triglyceride, total cholesterol, interleukin-6, and interleukin-10 levels were significantly higher in the OG, and serum high-density lipoprotein cholesterol level was significantly lower in the OG. Moreover, enhanced oxidative damage was observed in the pancreas, heart, spleen, lung, intestine, liver, and kidney. Evidence of an imbalanced antioxidant defense system, especially in the pancreas, spleen, and intestine, was observed in the obese AP rats. Compared with the OG, serum high-density lipoprotein cholesterol, interleukin-10, and superoxide dismutase expression levels in the pancreas, spleen, and intestine were increased in the SG. Additionally, SJP intervention led to a decrease in the following parameters: body weight; Lee's index; serum triglyceride levels; serum total cholesterol levels; malondialdehyde expression levels in the pancreas, heart, spleen, lung, and liver; myeloperoxidase expression levels in the lung; and pathological scores in the liver. CONCLUSION: Obesity may aggravate the inflammatory reaction and pathological multiple-organ injury in AP rats, and SJP may alleviate multiple-organ inflammatory injury in AP in rats fed a high-fat diet.

Sheng-Jiang Powder Ameliorates High Fat Diet Induced Nonalcoholic Fatty Liver Disease via Inhibiting Activation of Akt/mTOR/S6 Pathway in Rats.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem that directly contributes to increased prevalence of liver cirrhosis and hepatic cell cancer, but without any specific pharmacological option. Sheng-jiang powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great efficacy but the specific mechanisms have never been reported. Therefore, we performed this study to explore the effect of SJP on NAFLD and the potential mechanism. METHODS: NAFLD was induced by high fat diet (HFD) feeding. Rats were treated with SJP/normal saline daily for 10 weeks and all rats were euthanized after 12 weeks' feeding. Liver tissue samples were obtained for biochemistry test and pathological evaluation. Additionally, oleic acid induced LO2 cells were employed to simulate a cell model of NAFLD. Cells were subjected to western blotting for Akt, mTOR, S6, SREBP1-c, and FASN detection after coincubated with SJP, LY294002 (a selective PI3K inhibitor), or the combination for 24h. RESULTS: HFD significantly induced hepatic steatosis. Plenty of lipid droplets were observed under transmission electron microscope. The ultrastructure of liver cells showed distinct changes with obvious endoplasmic reticulum expansion, mitochondrial contraction, and cell matrix solidification. Although no difference was detected in serum hepatic enzymes and tissue proinflammatory cytokines, the tissue level of SOD and GSH-px was much lower and the pathologic injuries were much severe in HFD feeding rats. However, SJP treatment significantly attenuated the ultrastructure changes and protected rat liver against inflammatory injury. Abundant of lipid droplets and high expression of pAkt, pmTOR, pS6, and FASN were observed in oleic acid treated LO2 cells, while these changes were restored by SJP treatment. CONCLUSIONS: SJP is efficient in attenuating HFD induced NAFLD in rats and this effect might be partly related to the inhibition of Akt/mTOR/S6 pathway.

Sheng-jiang powder ameliorates obesity-induced pancreatic inflammatory injury via stimulating activation of the AMPK signalling pathway in rats.

AIM: To investigate the mechanisms by which Sheng-jiang powder (SJP) ameliorates obesity-induced pancreatic inflammatory injury. METHODS: Sprague-Dawley rats were randomized into three groups: normal group (NG), obese group (HLG), or SJP treatment group (HSG). Obesity was induced by feeding a high-fat diet in the HLG and HSG, while the NG received standard chow. Rats were euthanized after 12 wk, and blood and pancreatic tissues were collected for histopathological analyses. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-ß) expression, serum triglyceride and adiponectin levels, and apoptosis in pancreatic acinar cells were assessed. A high-fat AR42J acinar cell injury model was established using very low-density lipoprotein (VLDL). AR42J acinar cell culture supernatant, treated with different interventions, was applied to seven groups of pancreatic stellate cells (PSCs). The proliferation of PSCs and the expression of fibronectin and type I collagenase were assessed. RESULTS: Compared with the NG, we found higher pathological scores for pancreatic tissues, lower serum adiponectin levels, higher expression levels of NF-κB in pancreatic tissues and TGF-ß in pancreatic inflammatory cells, and increased apoptosis among pancreatic acinar cells for the HLG (P < 0.05). Compared with the HLG, we found reduced body weight, Lee's index scores, serum triglyceride levels, and pathological scores for pancreatic tissues; higher serum adiponectin levels; and lower expression levels of NF-κB, in pancreatic tissue and TGF-ß in pancreatic inflammatory cells for the HSG (P < 0.05). The in vitro studies showed enhanced PSC activation and increased expression levels of fibronectin and type I collagenase after SJP treatment. An adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor inhibited PSC activation. CONCLUSION: SJP may ameliorate obesity-induced pancreatic inflammatory injury in rats by regulating key molecules of the adiponectin-AMPK signalling pathway.

[Administration of Electroacupuncture and Da-Cheng-Qi Decoction Has a Synergetic Effect in Relieving Injury of Pancreas, Lung and Large Intestine and Inflammatory Reactions in Rats with Acute Pancreatitis].

OBJECTIVE: To explore the effectiveness of electroacupuncture (EA) stimulation of Shu-and Mu-points of Lung and Large Intestine Meridians combined with administration of Da-Cheng-Qi Decoction (DCQD) in the treatment of inflammatory injury in rats with acute pancreatitis, so as to reveal their synergetic anti-inflammatory effect. METHODS: Forty male SD rats were randomly divided into five groups: normal control, model, DCQD, EA, EA+DCQD, with 8 rats in each group. All the rats except those in the normal group received a retrograde biliopancreatic duct injection of sodium Taurocholate (3.0%, 0.1 mL/100 g) to induce an acute pancreatitis model. Twenty-four hours after modeling, EA (4 Hz/50 Hz) was applied to bilateral Shu-points "Feishu" (BL 13) and "Dachangshu" (BL 25), and Mu-points "Zhongfu" (LU 1) and "Tianshu" (ST 25) for 20 min, once every 7 h, 3 times in total. Rats of the DCQD and EA+DCQD groups were given intra-gastric gavage of DCQD (1 mL/100 g) 24 h after modeling, and those of the other 3 groups were given intra-gastric gavage of same dosage of normal saline. The histopathological changes of the pancreas, lung and large intestine tissues were observed after H. E. staining and scored according to Schmidt's and colleagues' methods (the severity of edema, inflammation, hemorrhage, necrosis). The concentrations of interleukin-6 (IL-6) and IL-10 in the serum, and those of myeloperoxidase (MPO) and malonaldehyde (MDA) in the lung and large intestine tissues were detected by using double-antibody sandwich ELISA. RESULTS: After modeling, the histopathological scores of pancreas, lung and large intestine tissues, the concentrations of MPO and MDA in lung and large intestine, and the levels of IL-6 and IL-10 in serum were significantly increased in the model group compared with the normal control group (P<0.05). Following the treatment, the histopathological scores of pancreas, lung and large intestine tissues, the contents of MPO and MDA in the lung and large intestine, and serum IL-6 were considerably reduced in the EA, DCQD and EA+DCQD groups relevant to the model group (P<0.05), while serum IL-10 content was notably increased in the three treatment groups (P<0.05). The therapeutic effect of EA+DCQD was significantly superior to that of simple EA and simple DCQD in down-regulating the histopathological scores of lung and large intestine tissues, the contents of MPO and MDA in the lung and large intestine, and serum IL-6 level, and up-regulating serum IL-10 level (P<0.05). No significant differences were found between the EA and DCQD groups in the above-mentioned 9 indexes (P>0.05). CONCLUSION: EA and DCQD can relieve the inflammatory injury of the pancreas, lung and large intestine tissues in rats with acute pancreatitis, and EA combined with DCQD has a better synergetic effect in reducing oxidative stress level and inflammatory reaction.

Effect of Da-Cheng-Qi decoction for treatment of acute kidney injury in rats with severe acute pancreatitis.

BACKGROUND: The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP). METHODS: Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC-MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated. RESULTS: Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased (p < 0.05). The high dose of DCQD showed a maximal effect in downregulating the pro-inflammatory mediators interleukin-6 (IL)-6 and tumour necrosis factor-α (TNF-α), upregulating anti-inflammatory mediators IL-4 and IL-10 in the kidney and alleviating the pathological damages. DCQD decreased the pancreas and kidney pathological scores of rats with SAP, especially in the HDG (p < 0.05). Compared with the MG, the level of Scr in the HDG was significantly decreased (p < 0.05). CONCLUSIONS: DCQD ameliorated AKI in rats with SAP via regulating the inflammatory response, which might be closely related to the distribution of its components in the kidney.

Effect of Sheng-Jiang Powder on Obesity-Induced Multiple Organ Injuries in Rats.

BACKGROUND AND AIMS: Obesity has become the main public health issue nowadays with poor control and has been associated with increased risk of multiorgan disease, but the specific mechanism and effective medication are still to be addressed. Sheng-jiang powder (SJP) showed great potential in preventing obesity in Chinese researches but has no trace in English reports. This study was designed to investigate the effect of SJP on obesity and obesity-mediated multiorgan injuries. METHODS: Rats were randomized into normal group (NG), obese group (OG), and SJP treatment group (SG). Obesity was induced by high-fat diet feeding. Rats were gavaged with SJP/normal saline daily from the third week and all rats were sacrificed after 12 weeks' feeding. Tissues were obtained for cytokines tests. RESULTS: Firstly, high-fat diet feeding led to significant obesity. Compared to NG, the level of SOD in the liver, spleen, lung, and kidney was much lower in OG (p < 0.05), while the pathological scores of pancreas, liver, spleen, lung, and kidney were much higher. SJP significantly increased SOD level in the liver, spleen, and lung and reduced the pathological scores of pancreas, liver, spleen, lung, and kidney correspondingly (p < 0.05). CONCLUSIONS: SJP ameliorates inflammatory response and mitigates obesity-induced multiple organ injuries.