Integrated pharmacokinetic properties and tissue distribution of multiple active constituents in Qing-Yi Recipe: A comparison between granules and decoction.

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated. Then, the integrated pharmacokinetic properties of Qing-Yi Recipe and its major metabolites in rats were investigated using the post-listed granules at both dosages. Subsequently, tissue distributions of those constituents in nine organs (especially the pancreas) were determined, and the overall parameters between the two formulations were compared. RESULTS: Though the chemical profiles of the formulas varied across formulations, the overall exposure level was very similar, and baicalin, wogonoside, geniposide, rhein, costunolide, and paeoniflorin were the top six bioactive compounds in the circulation. All twenty-two natural products reached their first peak within 2 h, and several of them exhibited bimodal or multimodal patterns under the complicated transformation of metabolic enzymes, and the parameters of these products markedly changed compared with those of monomers. Diverse metabolites of emodin and baicalin/baicalein were detected in circulation and tissues, augmenting the in vivo forms of these compounds. Finally, the enrichment of tetrahydropalmatine and corydaline in the pancreas were observed and most compounds remained in the gastrointestinal system, providing a foundation basis for their potential regulatory effects on the gut microbiota as well as the intestinal functions. CONCLUSION: Herein, the pharmacokinetic properties and tissue distribution of multiple potential active constituents in Qing-Yi Recipe were investigated at two dosages, providing a pharmacodynamic material basis of Qing-Yi Recipe for the first time. This investigation is expected to provide a new perspective and reference for future studies on the physiological disposition and potential pharmacodynamic basis of traditional Chinese medicine to treat acute abdomen diseases.

Qingyi granules ameliorate severe acute pancreatitis in rats by modulating the gut microbiota and serum metabolic aberrations.

CONTEXT: Qingyi granules can be used to effectively treat patients with severe acute pancreatitis (SAP). OBJECTIVE: To elucidate the role of gut microbiota-mediated metabolism in the therapeutic effects of Qingyi granules. MATERIALS AND METHODS: Sprague-Dawley rats were grouped into the sham operation, SAP model, Qingyi granule intervention (Q, 1.8 g/kg) and emodin intervention (E, 50 mg/kg) groups and observed for 24 h. H&E staining and ELISA were used for histopathological analysis and serum enzyme and cytokine assays. 16S rDNA sequencing and UHPLC-HRMS were used for gut microbiota analysis and untargeted metabolomics. RESULTS: In SAP rats, Qingyi granules decreased the pancreatic pathological score (Q, 7.4 ± 1.14; SAP, 11.6 ± 1.14, p < 0.01); serum amylase (Q, 121.2 ± 6.7; SAP, 144.3 ± 8.86, p < 0.05), lipase (Q, 566 ± 20.34; SAP, 656.7 ± 29.32, p < 0.01), and diamineoxidase (Q, 492.8 ± 26.08; SAP, 566.1 ± 26.83, p < 0.05) activities; and IL-1ß (Q, 29.48 ± 0.88; SAP, 36.17 ± 1.88, p < 0.01), IL-6 (Q, 112.2 ± 3.57; SAP, 128.9 ± 9.09, p < 0.05) and TNF-α (Q, 215.3 ± 8.67; SAP, 266.4 ± 28.03, p < 0.05) levels. SAP induced Helicobacter and Lactobacillus overgrowth and suppressed Romboutsia and Allobaculum growth and caused aberrations in bacterial metabolites, which were partly reversed by Qingyi granules. DISCUSSION AND CONCLUSIONS: Qingyi granules can modulate the gut microbiota and metabolic abnormalities to ameliorate SAP. Multi-omics approaches allow systematic study of the pharmacological mechanisms of compound prescriptions for critical illnesses.

Systematic characterization of Puerariae Flos metabolites in vivo and assessment of its protective mechanisms against alcoholic liver injury in a rat model.

Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound-target-pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4'-sulfate, tectoridin-4'-sulfate, and 6″-O-xylosyltectoridin-4'-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD.

Qingyi decoction attenuates intestinal epithelial cell injury via the calcineurin/nuclear factor of activated T-cells pathway.

BACKGROUND: Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis (SAP). A stable intestinal mucosa barrier functions as a major anatomic and functional barrier, owing to the balance between intestinal epithelial cell (IEC) proliferation and apoptosis. There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) signaling might play an important role in calcium-mediated apoptosis. AIM: To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction (QYD) in SAP. METHODS: A rat model of SAP was created via retrograde infusion of sodium deoxycholate. Serum levels of amylase, tumor necrosis factor (TNF-α), interleukin (IL)-6, D-lactic acid, and diamine oxidase (DAO); histological changes; and apoptosis of IECs were examined in rats with or without QYD treatment. The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative real-time polymerase chain reaction and western blotting. For in vitro studies, Caco-2 cells were treated with lipopolysaccharide (LPS) and QYD serum, and then cell viability and intracellular calcium levels were detected. RESULTS: Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase, TNF-α, and IL-6. Both the indicators of intestinal mucosa damage (D-lactic acid and DAO) and the levels of IEC apoptosis were elevated in the SAP group. QYD treatment reduced the serum levels of amylase, TNF-α, IL-6, D-lactic acid, and DAO and attenuated the histological findings. IEC apoptosis associated with SAP was ameliorated under QYD treatment. In addition, the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group, and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group. QYD significantly restrained CaN and NFATc3 gene expression in the intestine, which was upregulated in the SAP group. Furthermore, QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca2+ levels and inhibited cell death. CONCLUSION: QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated, at least partially, by restraining IEC apoptosis via the CaN/NFATc3 pathway.

Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis.

Impaired intestinal barrier function and gut microbiota dysbiosis are believed to be related to exacerbation of acute pancreatitis (AP). As a bacterial cell wall peptidoglycan component, diaminopimelic acid (DAP) is a specific ligand of NOD1 that regulates the NOD1/RIP2/NF-kB signaling pathway. Here, we investigated the role of DAP in the crosstalk between the gut microbiota and pancreas during the occurrence of AP. Upregulation of NOD1/RIP2/NF-kB and elevated serum DAP levels were found in severe AP (SAP) model rats. The accumulation of DAP in SAP patients corroborated its ability to serve as an indicator of disease severity. Subsequently, SAP rats were treated with oral administration of the traditional Chinese medicine Qingyi Keli (QYKL) as well as neomycin, which can widely eliminate DAP-containing bacteria. Both QYKL and neomycin intervention ameliorated intestinal and pancreatic damage and systemic inflammation in SAP rats. Through 16S rDNA sequencing, we found that QYKL could rehabilitate the gut microbiota structure and selectively inhibit the overgrowth of enteric bacteria, such as Helicobacter and Lactobacillus, in SAP rats without affecting some protective strains, including Romboutsia and Allobaculum. Interestingly, we demonstrated that the decrease in serum DAP was accompanied by suppression of the NOD1/RIP2/NF-kB signaling pathway in both the intestine and pancreas of the two intervention groups. Taken together, these results suggested that the gut microbiota-DAP-NOD1/RIP2 signaling pathway might play a critical role in the progression of AP and that SAP could be alleviated via intervention in the signaling pathway. Our work provides new potential early warning indicators of SAP and targets for intervention.

Artificial intelligence-directed acupuncture: a review.

Acupuncture is widely used around the whole world nowadays and exhibits significant efficacy against many chronic diseases, especially in pain-related diseases. With the rapid development of artificial intelligence (AI), its implementation into acupuncture has achieved a series of significant breakthroughs in many areas of acupuncture practice, such as acupoints selection and prescription, acupuncture manipulation identification, acupuncture efficacy prediction, and so on. The paper will discuss the significant theoretical and technical achievements in AI-directed acupuncture. AI-based data mining methods uncovered crucial acupoint combinations for treating various diseases, which provide a scientific basis for acupoints prescription in clinical practice. Furthermore, the rapid development of modern TCM instruments facilitates the integration of modern medical instruments, AI techniques, and acupuncture. This integration significantly improves the quantification, objectification, and standardization of acupuncture as well as the delivery of clinical personalized acupuncture therapy. Machine learning-based clinical efficacy prediction of acupuncture can help doctors screen patients who may benefit from acupuncture treatment. However, the existing challenges require additional work for developing AI-directed acupuncture. Some include a better understanding of ancient Chinese philosophy for AI researchers, TCM acupuncture theory-based explanation of the knowledge discoveries, construction of acupuncture databases, and clinical trials for novel knowledge validation. This review aims to summarize the major contribution of AI techniques to the discovery of novel acupuncture knowledge, the improvement for acupuncture safety and efficacy, the development and inheritance of acupuncture, and the major challenges for the further development of AI-directed acupuncture. The development of acupuncture can progress with the help of AI.

Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report.

BACKGROUND: Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We presented a case with NETs G1 of the hilar bile duct and the challenges for her treatment. CASE PRESENTATION: A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was Bismuth type II hilar cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathological and immunohistochemical examination indicated a perihilar bile duct NETs G1 with the microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 24 months without recurrence or disease progression. CONCLUSION: We know little of biliary NETs because of its rarity. There are currently no guidelines for the diagnosis and treatment of biliary NETs. We reported a case of perihilar bile duct NETs G1 with R1 resection, as far as we know this is the first report. More information about biliary NETs should be registered.

Effects of QingYi decoction on inflammatory markers in patients with acute pancreatitis: A meta-analysis.

INTRODUCTION: It is widely accepted that inflammatory responses play a key role in acute pancreatitis (AP). We conducted a systematic review and meta-analysis to determine the effect of QingYi decoction on inflammatory markers. METHODS: The PubMed, EMBASE, Cochrane, CNKI, CBM, and WANFGANG databases were searched for randomized controlled trials published before December 2019. Thirty-nine eligible studies were included in the meta-analysis. The quality of the included studies was assessed using the Cochrane Collaboration risk of bias tool. The standardized mean differences (SMDs) with corresponding 95% CIs were examined for inflammatory markers. The chi-square test and I2 statistic were used to assess heterogeneity. We assessed publication bias by Begg's test, Egger's test, and the trim and fill method. In addition, a meta-regression, sensitivity analysis, subgroup analysis, and cumulative meta-analysis were performed to assess the effects of confounding factors. The quality of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: The pooled effect estimate indicated that QingYi decoction treatment significantly reduced the levels of pro-inflammatory IL-6 (SMD = -3.33; 95% CI, -4.17, -2.50; p < 0.001; I2: 97.9%), IL-8 (SMD = -1.55; 95% CI, -2.03, -1.07; p < 0.001; I2: 96.1%), TNF-α (SMD = -1.04; 95% CI, -1.37, -0.72; p < 0.001; I2: 93.9%), IL-1 (SMD = -2.05; 95% CI, -3.21, -0.90; p < 0.001; I2: 93.4%), and IL-1ß (SMD = -1.31; 95% CI, -2.42, -0.21; p < 0.001; I2: 89.8%) and elevated the levels of anti-inflammatory IL-10 (SMD = 0.99; 95% CI, 0.60, 1.38; p < 0.001; I2: 91.1%) among patients with AP. CONCLUSION: The current review and meta-analysis suggest that the therapeutic effect of QingYi decoction may be related to its anti-inflammatory properties. Due to the high heterogeneity across the included studies, additional large-scale and rigorously designed studies are needed to confirm the conclusions of this study.

The Impact of Artificial Intelligence on Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is a well-established medical system with a long history. Currently, artificial intelligence (AI) is rapidly expanding in many fields including TCM. AI will significantly improve the reliability and accuracy of diagnostics, thus increasing the use of effective therapeutic methods for patients. This systematic review provides an updated overview on the major breakthroughs in the field of AI-assisted TCM four diagnostic methods, syndrome differentiation, and treatment. AI-assisted TCM diagnosis is mainly based on digital data collected by modern electronic instruments, which makes TCM diagnosis more quantitative, objective, and standardized. As a result, the diagnosis decisions made by different TCM doctors exhibit more consistency, accuracy, and reliability. Meanwhile, the therapeutic efficacy of TCM can be evaluated objectively. Therefore, AI is promoting TCM from experience to evidence-based medicine, a genuine scientific revolution. Furthermore, huge and non-uniform knowledge on formula-syndrome relationships and the combination rules of herbal TCM formulae could be better standardized with the help of AI analysis, which is necessary for the clinical efficacy evaluation and further optimization on the standardized TCM formulae. AI bridges the gap between TCM and modern science and technology. AI may bring clinical TCM diagnostics closer to western medicine. With the help of AI, more scientific evidence about TCM will be discovered. It can be expected that more unified guidelines for specific TCM syndromes will be issued with the development of AI-assisted TCM therapies in the future.

Effect of emodin on long non-coding RNA-mRNA networks in rats with severe acute pancreatitis-induced acute lung injury.

Long non-coding RNAs (lncRNAs) contribute to disease pathogenesis and drug treatment effects. Both emodin and dexamethasone (DEX) have been used for treating severe acute pancreatitis-associated acute lung injury (SAP-ALI). However, lncRNA regulation networks related to SAP-ALI pathogenesis and drug treatment are unreported. In this study, lncRNAs and mRNAs in the lung tissue of SAP-ALI and control rats, with or without drug treatment (emodin or DEX), were assessed by RNA sequencing. Results showed both emodin and DEX were therapeutic for SAP-ALI and that mRNA and lncRNA levels differed between untreated and treated SAP-ALI rats. Gene expression profile relationships for emodin-treated and control rats were higher than DEX-treated and -untreated animals. By comparison of control and SAP-ALI animals, more up-regulated than down-regulated mRNAs and lncRNAs were observed with emodin treatment. For DEX treatment, more down-regulated than up-regulated mRNAs and lncRNAs were observed. Functional analysis demonstrated both up-regulated mRNA and co-expressed genes with up-regulated lncRNAs were enriched in inflammatory and immune response pathways. Further, emodin-associated lncRNAs and mRNAs co-expressed modules were different from those associated with DEX. Quantitative polymerase chain reaction demonstrates selected lncRNA and mRNA co-expressed modules were different in the lung tissue of emodin- and DEX-treated rats. Also, emodin had different effects compared with DEX on co-expression network of lncRNAs Rn60_7_1164.1 and AABR07062477.2 for the blue lncRNA module and Nrp1 for the green mRNA module. In conclusion, this study provides evidence that emodin may be a suitable alternative or complementary medicine for treating SAP-ALI.

N-Ethyl-2-Pyrrolidinone-Substituted Flavan-3-Ols with Anti-inflammatory Activity in Lipopolysaccharide-Stimulated Macrophages Are Storage-Related Marker Compounds for Green Tea.

Fresh green tea (GT) is commonly considered to have better sensory flavor and higher commercial value than long-term-stored GT; however, the chemical variations during storage are unclear. In this study, the chemical profiles of stored GT were surveyed among time-series samples from 0 to 19 months using a nontargeted metabolomics method. Seven N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) increased from 0.022 ± 0.019 to 3.212 ± 0.057 mg/g within 19 months (correlation coefficients with storage duration ranging from 0.936 to 0.965), and they were the most significantly increased compounds among the 127 identified compounds. Two representative EPSFs (R-EGCG-cThea and S-EGCG-cThea) possess potential anti-inflammatory properties by suppressing the expression, phosphorylation, and nuclear translocation of nuclear factor kappa-B (NF-κB) p65 in lipopolysaccharide-stimulated macrophages based on western blotting and immunofluorescence results. In conclusion, EPSFs were found to be marker compounds for stored GT and showed potential anti-inflammatory activity by regulating the NF-κB signaling pathway.

Traditional Chinese Medicine as Potential Therapy for COVID-19.

In December 2019, a novel coronavirus SARS-CoV-2, causing the disease COVID-19, spread from Wuhan throughout China and has infected people over 200 countries. Thus far, more than 3,400,000 cases and 240,000 deaths have occurred worldwide, and the coronavirus pandemic continues to grip the globe. While numbers of cases in China have been steadying, the number of infections outside China is increasing at a worrying pace. We face an urgent need to control the spread of the COVID-19 epidemic, which is currently expanding to a global pandemic. Efforts have focused on testing antiviral drugs and vaccines, but there is currently no treatment specifically approved. Traditional Chinese medicine (TCM) is grounded in empirical observations and the Chinese people use TCM to overcome these sorts of plagues many times in thousands of years of history. Currently, the Chinese National Health Commission recommended a TCM prescription of Qing-Fei-Pai-Du-Tang (QFPDT) in the latest version of the "Diagnosis and Treatment guidelines of COVID-19" which has been reported to provide reliable effects for COVID-19. While doubts about TCM still exist today, this review paper will describe the rationalities that QFPDT is likely to bring a safe and effective treatment of COVID-19.

Hepatoprotective effect of plant polysaccharides from natural resources: A review of the mechanisms and structure-activity relationship.

Liver injury is a common pathological process, which can result in fatty liver, cirrhosis, fibrosis and even cancer. Polysaccharides isolated from plants have been regarded as an important resource of anti-hepatic lesion due to widely distributed in nature and low toxicity. In order to have a better understand of the protective mechanism on liver function, a comprehensive review of research into plant polysaccharides during recent five years was performed. In total, 66 types of polysaccharides from 58 kinds of plant have shown hepatoprotective effect through the pathological process of inflammation, apoptosis and oxidative stress by regulating NF-κB, JAK/STAT, TGF-ß, PI3K/AKT, MAPK, caspase cascade, p53 and Nrf2-Keap1 pathways, lipid metabolism as well as cytochrome P450 enzymes. Moreover, correlations between structure and hepatoprotective activities of plant polysaccharides including primary structure, conformation properties, structural modification and content of uronic acid were also preliminarily explored. This review will provide a comprehensive perspective for better understanding the mechanism and development of polysaccharides against liver injury.

Structurally Diverse Flavonolignans with Immunosuppressive and Neuroprotective Activities from the Fruits of Hippophae rhamnoides L.

The fruit of Hippophae rhamnoides L. has been used for centuries in Europe and Asia as a food with high nutritional and medicinal values. In this study, a bioactivity-guided phytochemical investigation of H. rhamnoides L. has resulted in four new dimethylallylated flavonolignans (1-4), four new isopropylpentenone-flavonolignan heterodimers (5-8), two new geranylated flavonolignans (9 and 10), and 14 known flavonolignan derivatives (11-24); they were elucidated by their spectrometric and spectroscopic methods, including HR-ESI-MS, NMR, IR, and UV from the fruit of H. rhamnoides L. for the first time. Among them, compounds 2, 5, 6, 20, and 21 showed potent immunosuppressive activities with IC50 values from 19.42 ± 3.91 to 48.05 ± 12.56 µM. Meanwhile, compounds 1, 4, 11, 12, and 13 showed moderate neuroprotective activities, which increased the cell survival rate from 50.30 ± 4.24% for the model group to 71.63 ± 3.04%, 70.02 ± 4.13%, 61.53 ± 5.93%, 61.08 ± 3.58%, and 65.68 ± 4.88% at 10 µM, respectively. The hypothetical biogenetic pathway and preliminary structure-activity relationship were found and discussed scientifically.

Berberine inhibits human gastric cancer cell growth via deactivation of p38/JNK pathway, induction of mitochondrial-mediated apoptosis, caspase activation and NF-κB inhibition.

PURPOSE: Gastric cancer accounts for considerable mortality across the globe. In this study the anticancer effects of a natural compound Berberine were investigated in vitro. Effects of berberine on cell migration, cellular apoptosis, Nf-kB and JNK/p38 signalling pathways were also studied. METHODS: The cell viability of SNU-1 gastric cancer cells after berberine treatment was evaluated by CCK-8 assay, while the effects on cell migration were checked by wound healing assay. Effects on cellular apoptosis were evaluated by fluorescence microscopy using DAPI staining, as well as using flow cytometry with annexin V/propidium iodide (PI) staining. Effects on apoptosis-related protein expressions were checked by western blot method. RESULTS: The results showed that Berberine decreased the viability of the gastric cancer SNU-1 cells and exhibited an IC50 of 30 µM. The cytoxicity of Berberine was also investigated on the normal GES-1 gastric cells and it was found that Berberine exerted very low toxic effects on these cells and exhibited an IC50 of 120 µM. Berberine also caused remarkable changes in the morphology of the SNU-1 cells. PI and DAPI staining revealed that Berberine prompted apoptosis of the SNU-1 cells in a dose-dependent manner. The apoptotic cells increased from 2.2% in control to around 35% at 30 µM concentration. Berberine also suppressed the migration and invasion of the gastric cancer cells via blocking of the JNK/p38 signalling pathway. CONCLUSIONS: Berberine may act as a promising drug candidate for gastric cancer as demonstrated from the current study.

Compounds of traditional Chinese medicine and neuropathic pain.

Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effective treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple components and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.

Compounds of traditional Chinese medicine and neuropathic pain / 中国天然药物

Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effective treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple components and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.

Interactions between artemisinin derivatives and P-glycoprotein.

BACKGROUND: Artemisinin was isolated and identified in 1972, which was the starting point for a new era in antimalarial drug therapy. Furthermore, numerous studies have demonstrated that artemisinin and its derivatives exhibit considerable anticancer activity both in vitro, in vivo, and even in clinical Phase I/II trials. P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) is one of the most serious causes of chemotherapy failure in cancer treatment. Interestingly, many artemisinin derivatives exhibit excellent ability to overcome P-gp mediated MDR and even show collateral sensitivity against MDR cancer cells. Furthermore, some artemisinin derivatives show P-gp-mediated MDR reversal activity. Therefore, the interaction between P-gp and artemisinin derivatives is important to develop novel combination treatment protocols with artemisinin derivatives and established anticancer drugs that are P-gp substrates. PURPOSE: This systematic review provides an updated overview on the interaction between artemisinin derivatives and P-gp and the effect of artemisinin derivatives on the P-gp expression level. RESULTS: Artemisinin derivatives exhibit multi-specific interactions with P-gp. The currently used artemisinin derivatives are not transported by P-gp. However, some of novel synthetized artemisinin derivatives exhibit P-gp substrate properties. Furthermore, many artemisinin derivatives act as P-gp inhibitors, which exhibit the potential to reverse MDR towards clinically used anticancer drugs. CONCLUSION: Therefore, studies on the interaction between artemisinin derivatives and P-gp provide important information for the development of novel anti-cancer artemisinin derivatives to reverse P-gp mediated MDR and for the design of rational artemisinin-based combination therapies against cancer.

Emerging Role of Chinese Herbal Medicines in the Treatment of Pancreatic Fibrosis.

Pancreatic fibrosis is the main pathologic characteristic in chronic pancreatitis (CP), a common disease that arises from surgery. Pancreatitis is caused by various etiologies, but the mechanism of fibrosis is not completely understood. Existing clinical approaches mainly focus on mitigating the symptoms and therefore do not cure the phenomena. In recent years, there has been a heightened interest in the use of Chinese herbal medicine (CHMs) in the prevention and cure of CP as expressed by increasing numbers of clinical and experimental research. Despite early cell culture and animal models, CHMs are able to interact with plenty of molecular targets involved in the pathogenesis of pancreatic fibrosis mostly via the TGF- ß /Smads pathway; however, integrated and up-to-date communication in this domain is unavailable. This review focuses on the research progress of CHMs against pancreatic fibrosis due to CP in vitro and in vivo and summarizes the potential mechanisms. We also outlined the toxicology of some CHMs for fibrosis treatment in order to provide a fuller understanding of drug safety. This review may provide reference for further innovative drug research and the future development of treatments for CP with pancreatic fibrosis.

Qingyi Decoction amerliorates acute biliary pancreatitis by targeting Gpbar1/NF-kb pathway.

Acute biliary pancreatitis (ABP) is a potentially life-threatening disease that is induced by the common bile duct (CBD) sludge or stones. This study aimed to investigate protective effects of Qingyi Decoction (QYT) on deoxycholic-acid-sodium salt (DCA) induced ABP in rats. Gpbar1 is a G-protein coupled receptor that can be activated by DCA. Both Gpbar1 overexpression vector and Gpbar1 RNAi were constructed and transfected into ABP cell models. Functional assays reveal that DCA significantly induced AR42J apoptosis and triggered Gpbar1 expression. Gpbar1 significantly activated caspase 8 and caspase 9 as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly triggered apoptosis associated inflammatory factors as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly induced calcium flux as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 up-regulated caspases and inflammatory factors in DCA treated pancreatic acinar cells. QYT reversed DCA induced apoptosis and inflammatory response. QYT significantly reduced Gpbar1 levels compared to no-QTY treated cells (p<0.05). In conclusion, QYT protects against DCA induced pancreatic acinar cell damage in ABP by inhibiting Gpbar1/NF-kB/p-RIP signaling pathway.