The American Journal of Chinese Medicine

Postoperative ileus is a common and often life-threatening gastrointestinal complication with few management methods available for patients. Integrating acupressure into perioperative care promises to bring benefits into preventing postoperative ileus. This systematic review and meta-analysis aims to evaluate the efficacy of acupressure in identifying the signs and symptoms of postoperative ileus among patients undergoing abdominal surgery. The MEDLINE, EMBASE, Web of Science, CINAHL, China Journal Net and Wanfang databases were searched for high-quality RCTs using keywords such as acupressure, postoperative ileus, abdominal surgery, etc. A total of six studies ($N=894$) were included in this review and meta-analysis. The quality of the literature was found to be uniformly moderate by the Effective Public Health Practice Project (EPHPP) assessment tool. The results of meta-analyses revealed that acupressure could significantly reduce risks for postoperative nausea (OR 0.52, 95% CI 0.39–0.70, $P<0.0001$) and vomiting (OR 0.54, 95% CI 0.39–0.75, $P<0.001$) compared with the control group, without significant heterogeneity among studies. Meta-analysis of the need for antiemetic drugs suggested that the OR was 0.39 (95% CI 0.20–0.78, $P<0.01$) with significant heterogeneity among studies. Our results suggested that acupressure might be effective in reducing the incidence of postoperative nausea and vomiting and the need for antiemetic drugs among patients undergoing abdominal surgery. Considering the substantial risk of bias in the articles included, future high-quality RCTs with a rigorous methodology are desirable to provide solid evidence. Furthermore, other signs and symptoms of postoperative ileus should be explored in future.

The first record of ginseng use dates back over two millennia, and ginseng is now popular in more than 35 countries. Ginsenosides are the pharmacological constituents responsible for the beneficial effects of ginseng. There is increasing evidence that ginseng and its bioactive ingredients are involved in the regulation of nuclear receptors, molecules that act in response to the specific binding of hormones, which link to a diverse array of signaling pathways, such as the ERK and PI3K/Akt pathways. Knowledge of the mechanism of how ginseng mediates these complexes is essential for the development of multi-target phytomedicine as possible therapy for different diseases. Here, we discuss the literature on the effects of ginseng and its constituents on estrogen, glucocorticoid, peroxisome proliferator-activated, and androgen nuclear hormone receptors, as well as how ginseng and its constituents exert their biological function in the treatment of cancer, obesity, and cardiovascular and neurological disorders. The accumulated results definitely show that the nuclear receptors are cellular targets of ginsenosides, but more rigorous data are required to establish and provide a scientific basis to confirm the suggested efficacy of ginseng or products with ginsenosides.

Astragalus membranaceus (Fisch) Bge (Huang-Qi) is a well-known herbal medicine with tonic property and has been widely used to treat cancer and other immune disorders in China and Southeast Asia for thousands of years. Accumulating evidence suggests that Huang-Qi possesses both immune-boosting and anti-inflammatory/immune-regulatory effects clinically, leaving the mechanism elusive. Recently, we discovered that Astragaloside (ASI), a major active component of Huang-Qi, is able to increase CD45 phosphatase activity. In this paper, we reviewed the recent progress of ASIs in immunoregulatory and anti-inflammatory activities, including the induction of T-cell activation, regulation of effector/regulatory T-cell balance, enhancement of CD45 phosphatase activity, inhibition of pro-inflammatory cytokine and, NF-$\kappa$B pathway. Finally, we hypothesized that inducing interferon-$\gamma$ (IFN-$\gamma$) activity by activating CD45 protein tyrosine phosphatase (PTPase) may be involved in the protective role of ASI in two contrary immune-associated diseases. These pharmacological properties highlight the traditional uses of Astragalus and provide a new direction for subsequent research and the clinical application of this traditional herbal.

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NF$\kappa$B/TNF$\alpha$/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NF$\kappa$B inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NF$\kappa$B/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases.

Salvianolic acid A (SAA), a polyphenols acid, is a bioactive ingredient from a traditional Chinese medicine called Dan shen (Salvia Miltiorrhiza Bunge). According to previous studies, it was shown to have various effects such as anti-oxidative stress, antidiabetic complications and antipulmonary hypertension. This study aimed to investigate the effect of SAA on pulmonary arterial endothelial–mesenchymal transition (EndoMT) induced by hypoxia and the underlying mechanisms. Primary cultured human pulmonary arterial endothelial cells (HPAECs) were exposed to 1% O₂ for 48h with or without SAA treatment. SAA treatment improved the morphology of HPAECs and inhibited the cytoskeleton remodeling. A total of 3$\mu$M SAA reduced migration distances from 262.2$\mu$m to 198.4$\mu$m at 24h and 344.8$\mu$m to 109.3$\mu$m at 48h. It was observed that the production of ROS in cells was significantly reduced by the treatment of 3$\mu$M SAA. Meanwhile, SAA alleviated the loss of CD31 and slightly inhibited the expression of $\alpha$-SMA. The mechanisms study shows that SAA treatment increased the phosphorylation levels of Smad1/5, but inhibited that of Smad2/3. Furthermore, SAA attenuated the phosphorylation levels of ERK and Cofilin, which were enhanced by hypoxia. Based on these results, our study indicated that SAA treatment can protect HPAECs from endoMT induced by hypoxia, which may perform via the inhibition on ROS production and further through the downstream effectors of BMPRs or TGF$\beta$R including Smads, ERK and ROCK/cofilin pathways.

Rhodiola crenulata root extract (RCE), a traditional Chinese medicine, has been shown to regulate glucose and lipid metabolism via the AMPK pathway in high glucose (HG) conditions. However, the effect of RCE on HG-induced endothelial dysfunction remains unclear. The present study was designed to examine the effects and mechanisms of RCE against hyperglycemic insult in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without RCE and then exposed to 33mM HG medium. The cell viability, nitrite production, oxidative stress markers, and vasoactive factors, as well as the mechanisms underlying RCE action, were then investigated. We found that RCE significantly improved cell death, nitric oxide (NO) defects, and oxidative stress in HG conditions. In addition, RCE significantly decreased the HG-induced vasoactive markers, including endothelin-1 (ET-1), fibronectin, and vascular endothelial growth factor (VEGF). However, the RCE-restored AMPK-Akt-eNOS-NO axis and cell viability were abolished by the presence of an AMPK inhibitor. These findings suggested that the protective effects of RCE were associated with the AMPK-Akt-eNOS-NO signaling pathway. In conclusion, we showed that RCE protected endothelial cells from hyperglycemic insult and demonstrated its potential for use as a treatment for endothelial dysfunction in diabetes mellitus.

The fruit body of artificially cultivated Cordyceps bassiana has been reported to exhibit anti-inflammatory and anticancer activities. Although it has been suggested that the fruit body has neutraceutic and pharmaceutic biomaterial potential, the exact anti-inflammatory molecular mechanism has not been fully elucidated. In this study, we demonstrated the immunopharmacologic activity of Cordyceps bassiana under in vitro conditions and investigated its anti-inflammatory mechanism. Water extract (Cm-WE) of the fruit body of artificially cultivated Cordyceps bassiana without polysaccharide fractions reduced the expression of the proinflammatory genes cyclooxygenase (COX)-2, interleukin (IL)-12, and inducible nitric oxide synthase (iNOS) and promoted the expression of the anti-inflammatory gene IL-10 in lipopolysaccharide (LPS)-treated RAW264.7 cells. In addition, this fraction suppressed proliferation and interferon (IFN)-$\gamma$ production in splenic T lymphocytes. Cm-WE blocked the activation of nuclear factor (NF)-$\kappa$B and activator protein (AP)-1 and their upstream inflammatory signaling cascades, including Syk, MEK, and JNK. Using kinase assays, Syk was identified as the target enzyme most strongly inhibited by Cm-WE. These results strongly suggest that Cm-WE suppresses inflammatory responses by inhibiting Syk kinase activity, with potential implications for novel neutraceutic and pharmaceutic biomaterials.

The present study evaluated the effects of heat-processed Scutellariae Radix (Scutellaria baicalensis) on lipopolysaccharide (LPS)-induced liver injury in mice. Scutellariae Radix heat-processed at 160${}^{\circ }$C or 180${}^{\circ }$C was orally administered at a dose of 100 mg/kg body weight for three days before the intraperitoneal injection of LPS, and the effects were compared with those of vehicle-treated LPS administered to control mice. The administration of Scutellariae Radix decreased the elevated serum monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), reactive oxygen species (ROS), nitrite/nitrate, peroxynitrite, and hepatic functional parameters, and reduced the increased ROS in the liver. The augmented expressions of hepatic oxidative stress and inflammation-related proteins, phospho-p38, phosphorylated extracellular signal-regulated kinase, phosphorylated c-Jun N-terminal kinase, nuclear factor-$\kappa$ B p65, activator protein-1, cyclooxygenase-2, inducible nitric oxide synthase, MCP-1, intercellular adhesion molecule-1, tumor necrosis factor-$\alpha$, and IL-6, were downregulated by the heat-processed Scutellariae Radix. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of LPS-treated mice improved with the administration of heat-processed Scutellariae Radix. Overall, the ameliorative effects of Scutellariae Radix were superior to those when heat-processed at 180${}^{\circ }$C. Our results indicate that heat-processed Scutellariae Radix acts as an anti-inflammatory agent by ameliorating oxidative stress in the liver of mice with LPS-induced liver injury.

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of severe sepsis or septic shock. In this study, we examined the effects of SFN on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. The anti-inflammatory activities of SFN were monitored based on its effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of SFN were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. SFN inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. SFN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with SFN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in vivo. Our results indicate that SFN is a possible therapeutic agent that can be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Lutein is a carotenoid with anti-oxidant properties. Autophagy, an evolutionarily conserved catabolic cellular pathway for coping with stress conditions, is responsive to reactive oxygen species (ROS) and degrades damaged organelles. We previously demonstrated that lutein can induce anti-oxidant enzymes to relieve methotrexate-induced ROS stress. We therefore hypothesized that lutein, which activates ROS-scavenging enzymes, can also induce autophagy for cell survival. In this study, we demonstrated that lutein treatment attenuated the reduction in cell viability caused by H₂O₂. Lutein dose-dependently induced the processing of microtubule-associated protein light chain 3 (LC3)-II, an autophagy marker protein, and accumulation of LC3-positive puncta in rat intestinal IEC-6 cells. Furthermore, (a) direct observation of autophagosome formation through transmission electron microscopy, (b) upregulation of autophagy-related genes including ATG4A, ATG5, ATG7, ATG12, and beclin-1 (BENC1), and (c) increased BECN1/Bcl-2 ratio confirmed the induction of autophagy by lutein. The results revealed that bafilomycin-A1-induced inhibition of autophagy reduced cell viability and increased apoptosis in lutein-treated cells, indicating a protective role of lutein-induced autophagy. Lutein treatment also activated adenosine monophosphate–activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK), and p-38, but had no effects on the induction of extracellular signal-related kinase or inhibition of mTOR; however, the inhibition of activated AMPK, JNK, or p-38 did not attenuate lutein-induced autophagy. Finally, increased BECN1 expression levels were detected in lutein-treated cells, and BECN1 knockdown abolished autophagy induction. These results suggest that lutein-induced autophagy was mediated by the upregulation of BECN1 in IEC-6 cells. We are the first to demonstrate that lutein induces autophagy. Elevated autophagy in lutein-treated IEC-6 cells may have a protective role against various stresses, and this warrants further investigation.

The root of Asian ginseng (Panax ginseng C.A. Meyer) has been used for centuries in Oriental medicine to improve general well-being and to relieve various medical conditions. It is commonly understood that ginsenosides are responsible for the pharmacological activities of ginseng. Compared to the root of ginseng, studies on the berry are considerably limited. In this study, we evaluated the effects of polysaccharides from Asian ginseng berries on plasma lipid levels, chemically-induced enteric inflammation and neoplasm, and cancer chemoprevention in different experimental models. We tested two polysaccharide preparations: regular ginseng berry polysaccharide extract (GBPE) and ginseng berry polysaccharide portion (GBPP, removed MV $<20,000$). We first observed that both oral GBPE and oral GBPP significantly reduced plasma cholesterol and triglycerides levels in a dose-related manner in ob/ob mice, without obvious body weight changes. Then, in AOM/DSS-induced acute colitis mice, GBPE and GBPP significantly ameliorated the increased gut disease activity index and inhibited the reduction of the colon length. Further, the berry polysaccharides significantly suppressed chemically-induced pro-inflammatory cytokine levels. This is consistent with the observation that GBPE and GBPP attenuated tumorigenesis in mice by significantly and dose-dependently reducing tumor load. Finally, in vitro HCT-116 and HT-29 human colon cancer cells were used. While these berry preparations had better antiproliferation effects on the HCT-116 than the HT-29 cells, the GBPE had significantly stronger inhibitory effects than GBPP. The observed in vitro GBPE’s effect could contribute to the actions of its small-molecule non-polysaccharide compounds due to their direct antiproliferative activities. Results obtained from the present study suggest that ginseng berry polysaccharides may have a therapeutic role in the management of high lipid levels, enteric inflammation, and colon malignancies.

Although Arctii Fructus (AF) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of AF on the metastatic properties of colorectal cancer (CRC). The aim of this study was to investigate whether AF could suppress CRC progression by inhibiting cell growth, epithelial-mesenchymal transition (EMT), migration, and the invasion ability of CRC cells. AF decreased proliferation of CRC cells by inducing cell cycle arrest and apoptosis via extrinsic and intrinsic apoptotic pathways. Regarding metastatic properties, AF inhibited EMT by increasing the expression of the epithelial marker, E-cadherin, and decreasing the expression of the mesenchymal marker, N-cadherin, in CT26 cells. Moreover, AF decreased the migration and invasion of CT26 cells by inhibiting matrix metalloproteinase-2 (MMP-2) and MMP-9 activity. We confirmed that the decreased invasion ability and MMP-9 activity by AF treatment involved AMP-activated protein kinase (AMPK) activation. Collectively, this study demonstrates that AF inhibits the proliferation and metastatic properties of CRC cells.