DCTPP1, a reliable Q-biomarker for comprehensive evaluation of the quality of tripterygium glycoside tablets based on chemical references.

BACKGROUND: As first-line clinical drugs, tripterygium glycoside tablets (TGTs) often have inconsistent efficacy and toxic side effects, mainly due to inadequate quality control. Therefore, clinically relevant quality standards for TGTs are urgently required. PURPOSE: Based on chemical substances and considering pharmacological efficacy, we aimed to develop an effective quality evaluation method for TGTs. METHODS: Representative commercial samples of TGTs were collected from different manufacturers, and qualitative UHPLC/LTQ-Orbitrap-MS and quantitative UHPLC-MS/MS analysis methods were successfully applied to evaluate their quality similarities and differences based on their chemical properties. Then the anti-immunity, anti-inflammatory and antitumor activities of TGTs and related monomers were evaluated using Jurkat, RAW264.7, MIA PaCa-2, and PANC-1 as cellular models. Subsequently, we predicted and verified small molecule-DCTPP1 interactions via molecular docking using the established DCTPP1 enzymatic activity assay. Finally, we performed a gray relational analysis to evaluate the chemical characteristics and biological effects of TGTs produced by different manufacturers. RESULTS: We collected 24 batches of TGTs (D01-D24) from 5 manufacturers (Co. A, Co. B, Co. C, Co. D, Co. E) for quality evaluation. The chemical composition analysis revealed significant differences in the substance bases of the samples. The D02, D18-D20 samples from Co. B constituted a separate group that differed from other samples, mainly in their absence of diterpenoids and triterpenoids, including triptolide, triptophenolide, and triptonide. In vitro anti-immunity, antitumor and anti-inflammatory tests using the same TGT concentration revealed that, except for D02, D18-D20, the remaining 20 samples exhibited different degrees of anti-immunity, antitumor and anti-inflammatory activity. Our experiments verified that triptolide, triptophenolide, and triptonide were all DCTPP1 inhibitors, and that TGTs generally exhibited DCTPP1 enzyme inhibitory activity. Moreover, the inhibitory activity of D02, D18-D20 samples from Co. B was much lower than that of the other samples, with a nearly tenfold difference in IC50. Further comprehensive analysis revealed a high correlation between DCTPP1 enzyme inhibition activity and the anti-immunity and antitumor and anti-inflammatory activities of these samples. CONCLUSION: The established DCTPP1 enzymatic activity assay proved suitable for quantitative pharmacological and pharmaceutical analysis to complement the existing quality control system for TGTs and to evaluate their effectiveness.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway.

OBJECTIVE: To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats. METHODS: Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1ß (IL-1ß) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3). RESULTS: Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1ß (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01). CONCLUSIONS: HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.

Bibliometric Study of Adaptogens in Dermatology: Pharmacophylogeny, Phytochemistry, and Pharmacological Mechanisms.

Background: Adaptogens are a class of medicinal plants that can nonspecifically enhance human resistance. Most of the plant adaptogens have relevant applications in dermatology, but there are still few studies related to their particular action and co-operative mechanisms in topical skin application. Methods: Plant adaptogens related articles and reviews that published between 1999 and 2022 were obtained from the Web of Science Core Collection database. Various bibliographic elements were collected, including the annual number of publications, countries/regions, and keywords. CiteSpace, a scientometric software, was used to conduct bibliometric analyses. Also, the patsnap global patent database was used to analyze the patent situation of plant adaptogens in the field of cosmetics up to 2021. Results: We found that the effects of plant adaptogens on skin diseases mainly involve atopic dermatitis, acne, allergic contact dermatitis, psoriasis, eczema, and androgenetic alopecia, etc. And the effects on skin health mainly involve anti-aging and anti-photoaging, anti-bacterial and anti-fungal, anti-inflammatory, whitening, and anti-hair loss, etc. Also, based on the results of patent analysis, it is found that the effects of plant adaptogens on skin mainly focus on aging retardation. The dermatological effects of plant adaptogens are mainly from Fabaceae Lindl., Araliaceae Juss. and Lamiaceae Martinov., and their mainly efficacy phytochemical components are terpenoids, phenolic compounds and flavonoids. Conclusion: The plant adaptogens can repair the skin barrier and maintain skin homeostasis by regulating the skin HPA-like axis, influencing the oxidative stress pathway to inhibit inflammation, and regulating the extracellular matrix (ECM) components to maintain a dynamic equilibrium, ultimately achieving the treatment of skin diseases and the maintenance of a healthy state.

Effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to post-traumatic stress disorder.

Data from clinical and experimental studies have verified the efficacy and safety of acupuncture in the treatment of post-traumatic stress disorder (PTSD). However, the concrete mechanism has not been well elucidated. The stress-induced activation of inflammatory response is involved in the development and pathogenesis of PTSD. Here, we aimed to investigate the effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to PTSD. Forty male rats were randomly divided into control, model, acupuncture and sertraline group. Within 1 day after adaptive feeding, all rats were exposed to single prolonged stress (SPS), except for the rats in the control group. Rats in acupuncture group were exposed to acupuncture intervention at the acupoints of Baihui (GV20) and Yintang (GV29), 20 min once per day for 15 days. Rats in sertraline group were exposed to a suspension of sertraline and distilled water (0.2 mg/ml), once per day for 15 days continuously. Body weight and elevated plus maze experiment were detected at different time-points to evaluate the behavioral changes of rats. HE staining method was used to observe the basic pathological morphological changes in hippocampus. Immunofluorescence staining method was used to observe the activation of hippocampal microglia. The content of IL-6 and IL-1ß in serum were detected by ELISA method. Compared with the control group, the body weight of rats in model group significantly decreased on 8 days, and the percentage of time in open arms and open arm entries decreased significantly on 15 days after SPS procedures, which indicated that SPS induced PTSD-like behavior in rats. Acupuncture exerted therapeutic effect. Simultaneously, the result of HE staining confirmed that SPS induced hippocampal morphological changes in SPS rats. Notably, acupuncture reversed the reduction and pathological injury to some extent. The results have also shown that acupuncture intervention effectively reversed the activated microglia of the hippocampus in rats. Moreover, the expression of IL-1ß in serum was significantly decreased by acupuncture intervention. In summary, the present study demonstrated that the role of acupuncture in eliminating PTSD-like behavior might be connected with reversing the pathological process of the inflammatory response mediated by the activation of microglia induced by SPS.

Acupuncture for brain diseases: Conception, application, and exploration.

The brain is probably the most complex organ in the human body. It has been the hot spot and direction of brain science research all over the world to deeply study the pathogenesis of various kinds of brain diseases and find effective treatment methods. Acupuncture is a nonpharmacological therapy of traditional Chinese medicine originating from ancient clinical practice. The research on the treatment of brain diseases by acupuncture has been constantly enriched and updated with the promotion of interdisciplinary research. In order to account for the current achievements in the field of acupuncture for brain diseases, this article reviews it in terms of conception, application, and exploration. Based on the literature review, we found that in the past decades, acupuncture has received widespread attention worldwide and many literatures have reported the clinical efficacy and underlying mechanisms of acupuncture in the treatment of brain diseases. Presently, the conception, application, and exploration of acupuncture in the treatment of brain diseases have evolved from empirical medicine to evidence-based medicine and precision medicine, and are experiencing a deeper understanding of the information about acupuncture regulating the brain function based on interdisciplinary research.

Anticonvulsant Activity of Bombyx batryticatus and Analysis of Bioactive Extracts Based on UHPLC-Q-TOF MS/MS and Molecular Networking.

Bombyx batryticatus (BB) is an anticonvulsant animal medicine in traditional Chinese medicine (TCM) and acts on the central nervous system. This research aimed to study the anticonvulsant effects of different polarity fractions of extracts from BB and to explore the components conferring anticonvulsant activity. Materials and methods: Crude extracts of BB at 20 g/kg were divided into different polarity fractions (petroleum ether, chloroform, ethyl acetate, water) and were administered to groups of mice before injecting pentylenetetrazol (PTZ) to induce convulsions. The animals were placed in chambers, and their behaviors were recorded for 30 min following the injection. Latency time, percent of protection, convulsion, convulsion rate, and convulsion score were determined for these mice. The compounds present in the different fractions were analyzed, and those from the fraction that conferred anticonvulsant activity were identified by high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF MS) and molecular networking (MN). The chloroform extract fractions (B-C) clearly increased the seizure latency time and protection percentage and decreased the convulsion percentage compared to the control group. The anticonvulsant effect of other extract fractions was not significant. Our study shows that the chloroform extract fractions (B-C) of BB have a significant anticonvulsant effect. We also identified 17 compounds including lumichrome, pheophorbide A, and episyringaresinol 4'-O-beta-d-glucopyranose that were found for the first time. The results of this study may lay the groundwork for studying compounds derived from Bombyx batryticatus and their anticonvulsant effect.

Acupuncture Ameliorates Depressive Behaviors by Modulating the Expression of Hippocampal Iba-1 and HMGB1 in Rats Exposed to Chronic Restraint Stress.

The antidepressant mechanism of acupuncture has not been fully elucidated recently. Thus, the objective of the present study is to investigate the antidepressant mechanism of acupuncture of modulating the neuroinflammation induced by high mobility group box-1 (HMGB1) in rats subjected to chronic restraint stress (CRS). Forty-four male Sprague Dawley rats were randomly divided into control, model, escitalopram, and acupuncture group. Except for rats in the control group, all rats were exposed to CRS for 21 days continuously. Rats in the escitalopram group were subjected to a suspension of escitalopram and saline. One hour before CRS procedures, acupuncture was performed at Baihui (GV20) and Yintang (GV29) for rats in the acupuncture group, 20 min per day for 21 days. All rats in each group were conducted to detect the body weight, sucrose preference test at 0, 7, 14, 21 days to evaluate the depression-like behaviors. The expression of microglial activation and HMGB1 in the hippocampus was detected by immunofluorescence. The expression of hippocampal interleukin-10 (IL-10) was detected by western blot. And the content of serum tumor necrosis factor-α (TNF-α) was detected by the enzyme-linked immunosorbent assay method. CRS-exposed rats showed obviously decreased body weight and sucrose preference when compared with the control group, which was reversed by acupuncture. The results have also shown that acupuncture ameliorated the CRS-induced activation of microglia and HMGB1 in the hippocampus CA1 region. Furthermore, acupuncture reduced the stress-induced upregulation of TNF-α in serum. Collectively, the current study highlights the role of acupuncture in alleviating depressive behavior associated with stress-induced neuroinflammation mediated by HMGB1 in the CRS model of depression.

[Priority ranking of Chinese patent medicine prescriptions for type 2 diabetes mellitus (syndrome of deficiency of both Qi and Yin): based on analytic hierarchy process (AHP)].

Clinical expertise, patient preference, and the best evidence are the three elements of evidence-based medicine. Based on high-level and high-quality evidence, qualitative and quantitative analysis of the prescribing decisions of physicians is beneficial to improving clinical efficacy. A mature methodological system is available for the retrieval, analysis, summary, evaluation, and recommendation of the evidence, but there are still few studies on physicians' prescribing decisions. How to analyze the trend of physicians' prescribing decisions based on the priority ranking in addition and subtraction of prescriptions? Analytic hierarchy process(AHP) is a method for decision making, which arranges the elements of the decision problem into overall goal, criteria, and operational sub-criteria, and uses the matrix eigenvector method to solve the problem. This study aims to analyze the priority of physicians' prescribing decisions for diabetes mellitus with deficiency of both Qi and Yin based on AHP. To be specific, a database of diabetes mellitus cases with deficiency of both Qi and Yin was established and AHP was used to yield the priority ranking of Chinese patent medicine prescriptions in specific clinical scenarios. In the selected cases of diabetes mellitus with deficiency of both Qi and Yin, Xiaoke Pills was the best prescription for the treatment of type 2 diabetes mellitus(deficiency of both Qi and Yin)(normalized=0.388), followed by Liuwei Dihuang Pills(normalized=0.269), Qishen Capsules(normalized=0.230), and Shengmai Injection(normalized=0.113). According to the analysis the available data, for type 2 diabetes mellitus(deficiency of both Qi and Yin), Xiaoke Pills was the most effective prescription in specific scenarios. When the physicians' prescribing decisions are consistent with the evidence, quantitative analysis of physicians' cognition will boost the evidence-based medical decision-making. However, the research results are also affected by the quality of literature, evidence level and priority, which are thus have some limitations. It is recommended that further small data research based on individual cases be carried out to lay a evidence-based basis for the clinical decision-making of type 2 diabetes mellitus.

Bibliometric analysis of the effects of ginseng on skin.

OBJECTIVE: Ginseng is widely used in cosmetics and skin care. The progress of research on the effect of ginseng on the skin was explored through a summary and analysis of skin-related studies on ginseng conducted over in the past 20 years, and this exploration aimed to elucidate new research opportunities with regard to the development and application of ginseng treatments for the skin. MATERIALS AND METHODS: Keywords were used to retrieve human studies related to the use of ginseng to treat skin conditions from the Web of Science. Scientometric analyses were performed in R to analyze the studies on the human skin-related effects of ginseng conducted from 2000 to 2019. RESULTS: The main active ingredient in ginseng is ginsenoside, and its effects on the skin are mostly anti-aging and whitening. Ginseng extract regulates the levels of matrix metalloproteinases in human fibroblast type I collagen to improve the elasticity and water content of skin. In addition, ginseng inhibits the transcription factors or signaling pathways involved in the formation of melanin, it exerts a whitening effect. The authors of the retrieved studies are mostly located in Asia, mainly South Korea and China. Wang Y, Kim JH, and Kim YJ are relatively influential scholars, these ginseng-related articles published in the Journal of Ginseng Research, Molecules and other journals are very important in this field. CONCLUSION: This study shows the development of trends in research on ginseng as a raw cosmetic material used on the skin and thus enables researchers to rapidly understand the key information in the field of ginseng research, comprehend the research directions, and improve their research efficiency.

[Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine].

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.

Efficacy and safety of acupuncture in the treatment of depression: A systematic review of clinical research.

As a common mental disorder, depression is one of the leading causes of disability around the world. Clinical studies have shown that acupuncture is an effective therapy without obvious side effects compared to limited efficacy and adverse reactions of drug therapy, cognitive behavioral therapy, and neuromodulation technology in treating depression. The objective of this review is to systematically evaluate whether acupuncture therapies for depression are safe and effective in order to provide a high-quality reference for clinical trials of acupuncture. A systematic search of the literature was carried out through bibliographic search engine PubMed. Subsequently, the study design, intervention methods, control group, results, and safety of acupuncture were analyzed. The results showed that acupuncture as an adjunct to antidepressants or as a single treatment can exert a positive impact on patients' depressive symptoms. Compared with antidepressants, acupuncture has the advantages of fast onset and long-term efficacy in the treatment of depression, and can enhance the efficacy of antidepressants. Moreover, the efficacy and safety of acupuncture in the treatment of depression maybe related to the qualification of the acupuncturist, the selection of acupoints, and intervention measures.

Effects of transcutaneous auricular vagus nerve stimulation on brain functional connectivity of medial prefrontal cortex in patients with primary insomnia.

As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI.

A metabolomic approach to elucidate the inhibitory effects of baicalin in pulmonary fibrosis.

CONTEXT: Baicalin, a major flavonoid extracted from Scutellaria baicalensis Georgi (Lamiaceae), has been shown to exert therapeutic effects on pulmonary fibrosis (PF). OBJECTIVE: To use serum metabolomics combined with biochemical and histopathological analyses to clarify anti-PF mechanisms of baicalin on metabolic pathways and the levels of potential biomarkers. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were randomly divided into the control, PF model, prednisolone acetate-treated (4.2 mg/kg/day) and baicalin-treated (25 and 100 mg/kg/day) groups. A rat model of PF was established using a tracheal injection of bleomycin, and the respective drugs were administered intragastrically for 4 weeks. Histomorphology of lung tissue was examined after H&E and Masson's trichrome staining. Biochemical indicators including SOD, MDA and HYP were measured. Serum-metabonomic analysis based on UPLC-Q-TOF/MS was used to clarify the changes in potential biomarkers among different groups of PF rats. RESULTS: Both doses of baicalin effectively alleviated bleomycin-induced pathological changes, and increased the levels of SOD (from 69.48 to 99.50 and 112.30, respectively), reduced the levels of MDA (from 10.91 to 5.0 and 7.53, respectively) and HYP (from 0.63 to 0.41 and 0.49, respectively). Forty-eight potential biomarkers associated with PF were identified. Meanwhile, the metabolic profiles and fluctuating metabolite levels were normalized or partially reversed after baicalin treatment. Furthermore, baicalin was found to improve PF potentially by the regulation of four key biomarkers involving taurine and hypotaurine metabolism, glutathione metabolism, and glycerophospholipid metabolism. CONCLUSIONS: These findings revealed the anti-fibrotic mechanisms of baicalin and it may be considered as an effective therapy for PF.

[Network Meta-analysis of clinical efficacy of Chinese herbal injection in adjuvant treatment of unstable angina pectoris].

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.

Near-infrared inorganic nanomaterial-based nanosystems for photothermal therapy.

The development of robust materials for treating diseases through non-invasive photothermal therapy (PTT) has attracted increasing attention in recent years. Among various types of nanomaterials, inorganic nanomaterials with strong absorption in the near-infrared (NIR) window can be employed as high-efficiency photothermal agents to treat cancer and bacterial infections. In addition, inorganic nanomaterials can be easily combined with other drugs or chemical reagents to construct multifunctional nanomaterials to cascade stimulation responses, enhance therapeutic effects, and perform precise medical treatments. In this review, focusing on the latest developments of inorganic nanomaterials in photothermal therapy, we firstly introduced the light-to-heat conversion mechanism of inorganic nanomaterials. Secondly, we summarized the application of common inorganic nanomaterials, such as metallic nanoparticles, transition metal oxide nanoparticles and two dimensional (2D) nanosheets. In addition, the strategy of developing multifunctional nano-platforms with excellent biocompatibility as well as good targeted capability was also expounded. Finally, challenges and new perspectives for designing effective inorganic nanomaterial-based nanosystems for photothermal assisted therapy were also discussed.

Mechanism of 'Invigorating Qi and Promoting Blood Circulation' Drug Pair Ginseng-Danshen on Treatment of Ischemic Heart Disease Based on Network Pharmacology.

OBJECTIVE: Using network pharmacology to explore the mechanism of the 'invigorating qi and promoting blood circulation' drug pair Ginseng-Danshen (Salvia miltiorrhiza) on treatment of ischemic heart disease (IHD). METHODS: The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential targets of the pair were identified. The pharmacodynamics of the pair was analyzed using network pharmacology. The targets of IHD were identified by database screening. Using protein-protein interaction network, the interaction targets of Ginseng-Danshen on IHD were constructed. A "constituent-target-disease" interaction network was constructed using Cytoscape software, Gene Ontology (GO) term enrichment analysis and biological pathway enrichment analysis were carried out, and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated. RESULTS: Seventeen active constituents and 53 targets were identified from ginseng, 53 active constituents and 61 targets were identified from Danshen, and 32 protein targets were shared by ginseng and Danshen. Twenty GO terms were analyzed, including cytokine receptor binding, cytokine activity, heme binding, and antioxidant activity. Sixty Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were analyzed, including phosphatidylinositol 3-kinase-serine-threonine kinase (PI3K-AKT) signaling pathway, p53 signaling pathway, interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, and the advanced glycation end product (AGE)-the receptor for AGE (RAGE) signaling pathway in diabetic complications. CONCLUSION: The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody, inhibiting the production of peroxides, removing the endogenous oxygen free radicals, regulating the expression of inflammatory factors, reducing myocardial cell apoptosis and promoting vascular regeneration.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Peripheral and Central Tumor Necrosis Factor Alpha in Rats with Depression-Chronic Somatic Pain Comorbidity.

Depression and pain disorders share a high degree of comorbidity. Inflammatory mechanisms play an important role in the pathogenesis of depression-chronic somatic pain comorbidity. In this study, we investigated the effects of acupuncture on blood and brain regional tumor necrosis factor alpha (TNF-α) in rats with depression and chronic somatic pain comorbidity. Forty Sprague-Dawley rats were randomly divided into the following 4 groups with 10 each: control, model, model treated with transcutaneous auricular vagus nerve stimulation (taVNS), and model treated with electroacupuncture (EA). Chronic unpredictable mild stress (CUMS) with chronic constriction injury of the sciatic nerve (CCI) was used to produce depression and chronic somatic pain comorbidity in the latter 3 groups. The rats of the taVNS and EA groups received, respectively, taVNS and EA at ST 36 for 28 days. Pain intensity was measured using a mechanical withdrawal threshold and thermal stimulation latency once biweekly. Depressive behavior was examined using a sucrose preference test at baseline and the end of modeling and intervention. The level of plasma TNF-α and the expression of TNF-α in the prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus were measured. While CUMS plus CCI produced remarkable depression-like behavior and pain disorders, EA and taVNS significantly improved depression and reduced pain intensity. CUMS plus CCI also resulted in a significant increase in plasma TNF-α level and the expression in all brain regions examined compared to the intact controls. Both EA and taVNS interventions, however, suppressed the elevated level of TNF-α. These results suggest that EA and taVNS have antidepressant and analgesic effects. Such effects may be associated with the suppression of TNF-α-related neuroinflammation.

Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles.

The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

[Effect of wrist-ankle acupuncture on the expression of glutamate and NMDA receptor of the spinal dorsal horn in rats with neuropathic pain].

OBJECTIVE: To observe the effect of wrist-ankle acupuncture (WA) stimulation at "R4"- "R5" - "R6" on the expression of glutamate (Glu) and phosphorylated protein NMDAR1(p-NMDAR1) of the spinal dorsal horn in spared nerve injury (SNI) rats, so as to explore its mechanism underlying improvement of SNI. METHODS: A total of 36 SD rats were randomly divi-ded into sham operation, model and WA groups, with 12 rats in each group. The SNI procedure comprised an axotomy and ligation of the tibial and common peroneal nerves leaving the sural nerve intact. Rats of the WA group were treated by acupuncture at "R4"-"R5"-"R6" points from the 5th day to the 14th day after modeling. The mechanical pain thresholds were measured before and 5, 10 and 14 d after SNI, respectively. The cold allodynia was dectected by Acetone solution dropped onto the lateral plantar surface of the paw. Glu content and p-NMDAR1 expression of spinal dorsal horn were detected by 1H-MRS, ELISA and immunohistochemistry Methods. RESULTS: Compared with the sham operation group, the mechanical pain threshold of the model group was significantly decreased (P<0.01), the duration of cold stimulation foot contraction was increased (P<0.01), and the Glu content and p-NMDAR1 expression in the spinal dorsal horn were significantly increased (P<0.05, P<0.01). After WA intervention, the mechanical pain threshold was significantly increased (P<0.01), the duration of cold stimulation was significantly shortened (P<0.01), and Glu content and p-NMDAR1 protein expression of spinal dorsal horn were decreased significantly (P<0.05, P<0.01) in the WA group compared with the model group. CONCLUSION: WA can reduce pain sensitivity in rats with neuropathic pain, possibly by inhibiting the expression of Glu and p-NMDAR1 in the spinal dorsal horn.

[Research progress of traditional Chinese medicine in regulating autophagy and ischemic heart disease].

Ischemic heart disease(IHD) is a common and frequently-occurring disease that causes serious harm to human health. Autophagy is a life process that maintains cell homeostasis by degrading macromolecules such as damaged organelles in cells. In the process of ischemic heart disease development, on the one hand, cardiomyocytes degrade macromolecules such as damaged organelles by autophagy to provide material basis for energy synthesis and maintain cell homeostasis; on the other hand, over-activated autophagy can also increase cardiomyocyte death. Ischemic heart disease has a complex pathological mechanism, and the occurrence of autophagy is closely related to the survival or death of myocardial cells, so the regulation of autophagy may be an important therapeutic target for ischemic heart disease. Traditional Chinese medicine(TCM) with obvious effects, unique advantages and great potential has been widely used in the treatment of ischemic heart disease. In recent years, more and more studies have found that TCM can protect myocardium by regulating autophagy of cardiomyocytes. In this review, we summarized recent studies on the regulation of autophagy in myocardial cells by traditional Chinese medicine in ischemic heart disease. The pharmacological mechanism of Chinese medicinein regulating autophagy to protect cardiomyocytes was reviewed through different ways(promoting or inhibiting autophagy) from three levels, i.e. active ingredient, as well as drug pair and compound. The specific mechanism of Chinese medicine in regulating autophagy to protect ischemic heart disease was explored to provide references or new ideas for clinical treatment and drug development of ischemic heart disease.