Visual analysis on the study status and trends of acupuncture and moxibustion for Alzheimer's disease. / é’ˆç¸æ²»ç–—é˜¿å°”èŒ¨æµ·é»˜ç— ç ”ç©¶çŠ¶å†µåŠè¶‹åŠ¿çš„å¯è§†åŒ–åˆ†æž.

The research history, hot spots and frontier trends of acupuncture and moxibustion for Alzheimer's disease (AD) were explored using knowledge graph technology. The articles on acupuncture and moxibustion for AD were searched from 6 databases, i.e. CNKI, VIP, Wanfang, SinoMed, Pubmed and Web of Science, from January 1st, 1993 to January 1st, 2023. Using CiteSpace6.2.R2 Advance and VOSviewer V1.6.19 softwares, the knowledge map was graphed and the visual analysis was performed. A total of 1 228 Chinese and 309 English articles were included. The high-frequency keywords were generally divided into the keywords of clinical diseases (AD, dementia), those of therapeutic methods (electroacupuncture, acupuncture-moxibustion and acupuncture) and those of mechanism study (ß-amyloid, mice). Thirteen keyword clusters were formed among the articles of Chinese version, e.g. acupuncture-moxibustion, dementia, acupuncture and electroacupuncture; and 8 clusters were obtained among English articles, e.g. electroacupuncture, drug therapy and hippocampus. The high-frequency keywords of acupoints included Baihui (GV 20), Dazhui (GV 14), Yintang (GV 24+), Zusanli (ST 36), Fenglong (ST 40), etc. Six clusters of "acupuncture techniques → acupoints" were obtained for the treatment of AD with acupuncture and moxibustion. The therapeutic methods and modes of AD with acupuncture and moxibustion are constantly progressed, the development of clinical research tends to the evaluation of novel therapeutic mode and clinical effect, and the mechanism of acupuncture and moxibustion for the effect on AD are more deeply explored. Among the various therapeutic methods, acupuncture-moxibustion, acupuncture and electroacupuncture have been early predominant; while, many novel methods are gradually displayed later, such as music electroacupuncture and hydro-acupuncture. In recent 30 years, among Chinese and English articles for the studies of AD treated with acupuncture and moxibustion, the theme of them focuses on the two aspects, the observation of clinical effect and the mechanism research. It is found that the clinical therapeutic methods have been gradually improved and the mechanism exploration been deepened.

Comprehensive consideration of multiple determinants from evidence to recommendations in guidelines for most traditional Chinese medicine was suboptimal: a systematic review.

BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.

Out-of-set association analysis of lung cancer drugs and symptoms based on clinical case data mining.

BACKGROUND: There are 1.8 million lung cancer deaths worldwide, accounting for 18% of global cancer deaths, including 710,000 in China, accounting for 23.8% of all cancer deaths in China. OBJECTIVE: To explore the out-of-set association rules of lung cancer symptoms and drugs through text mining of traditional Chinese medicine (TCM) treatment of lung cancer, and form medical case analysis to analyze the experience of TCM syndrome differentiation in its treatment. METHODS: The medical records of all patients diagnosed with lung cancer in Nanjing Chest Hospital from January to December 2018 were collected, and the out-of-set association analysis was performed using the MedCase v5.2 TCM clinical scientific research auxiliary platform based on the frequent pattern growth enhanced association analysis algorithm. RESULTS: In terms of TCM treatment of lung cancer, the clinical symptoms with high correlation included cough, expectoration, chest distress, and white phlegm; and the drugs with high correlation included Pinellia ternata, licorice root, white Atractylodes rhizome, and Radix Ophiopogonis; with the prescriptions based on Erchen and Maimendong decoctions. CONCLUSION: This analytical study of the medical cases of TCM treatment for lung cancer was performed using data mining techniques, and the out-of-set association rules between clinical symptoms and drugs were analyzed, including the understanding of lung cancer in TCM. Moreover, the essence of experience in drug use was gathered, providing significant scientific guidance for the clinical treatment of lung cancer.

Celastrus orbiculatus extract suppresses gastric cancer stem cells through the TGF-ß/Smad signaling pathway.

Cancer stem cells (CSCs) are the primary source of tumor recurrence and chemoresistance, which complicates tumor treatment and has a significant impact on poor patient prognosis. Therefore, the discovery of inhibitors that specifically target CSCs is warranted. Previous research has established that the TGF-ß/Smad signaling pathway is critical for the maintenance of CSCs phenotype, thus facilitating CSCs transformation. In this regard, Celastrus orbiculatus ethyl acetate extract (COE) was shown to exert anticancer properties; however, its therapeutic impact on gastric cancer stem cells (GCSCs) remains unknown. We here demonstrate that COE displayed a strong inhibitory effect on GCSCs growth and CSCs markers. Moreover, COE was shown to efficiently inhibit the development of tumor spheres and accelerate GCSCs apoptosis. Mechanistically, we established that COE could suppress the stemness phenotype of GCSCs by inhibiting the activity of the TGF-ß/Smad signaling pathway. To summarize, our data indicate that COE suppresses the malignant biological phenotype of GCSCs via the TGF-ß/Smad signaling pathway. These findings shed new light on the anticancer properties of COE and suggest new strategies for the development of efficient GCSCs therapeutics.

1,25(OH)2D3 alleviates oxidative stress and inflammation through up-regulating HMGCS2 in DSS-induced colitis.

BACKGROUND: Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS: HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS: Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION: 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.

Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study.

BACKGROUND: Trials have demonstrated lower rates of acute kidney injury in critically ill patients receiving magnesium supplementation, but they have yielded conflicting results regarding mortality. METHODS: This is a retrospective cohort study based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with sepsis were included in the analysis. The exposure was magnesium sulfate use during ICU stay. The primary outcome was 28-day all-cause mortality. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders. RESULTS: The pre-matched and propensity score-matched cohorts included 10 999 and 6052 patients, respectively. In the PSM analysis, 28-day all-cause mortality rate was 20.2% (611/3026) in the magnesium sulfate use group and 25.0% (757/3026) in the no use group. Magnesium sulfate use was associated with lower 28-day all-cause mortality (hazard ratio [HR], 0.70; 95% CI, 0.61-0.79; P<0.001). Lower mortality was observed regardless of baseline serum magnesium status: for hypomagnesaemia, HR, 0.64; 95% confidence interval (CI), 0.45-0.93; P=0.020; for normomagnesaemia, HR, 0.70; 95% CI, 0.61-0.80; P<0.001. Magnesium sulfate use was also associated with lower ICU mortality (odds ratio [OR], 0.52; 95% CI, 0.42-0.64; P<0.001), lower in-hospital mortality (OR, 0.65; 95% CI, 0.55-0.77; P<0.001), and renal replacement therapy (OR, 0.67; 95% CI, 0.52-0.87; P=0.002). A sensitivity analysis using the entire cohort also demonstrated lower 28-day all-cause mortality (HR, 0.62; 95% CI, 0.56-0.69; P<0.001). CONCLUSIONS: Magnesium sulfate use was associated with lower mortality in critically ill patients with sepsis. Prospective studies are needed to verify this finding.

Cynanchum komarovii extract for the treatment of rheumatoid arthritis by acting on synovial cells in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii (CK), the northwest Chinese region's common medicinal herb, was traditionally utilized to treat arthritis, toothache, bald sores and cholecystitis. Various forms of arthritis can be treated with CK, based on "Medicinal Plants of Chinese Desert Areas". However, the exact mechanism of action in rheumatoid arthritis (RA) is uncertain. AIM OF THE STUDY: To evaluate the in vitro and in vivo effects of CK extracts on RA and to preliminarily investigate its anti-RA mechanism of action. MATERIALS AND METHODS: The main components of CK extract were analyzed by HPLC method. The effects of CK on the proliferation and apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes (HFLS-RA) cells and the expression of apoptosis-related proteins in HFLS-RA cells were evaluated by CCK8 assay, flow cytometry and WB assay. To verify the anti-RA effect of CK extracts in vivo, a collagen-induced arthritis (CIA) rat model was established. The rats were divided into six groups: normal group, model group, CK high-dose group (1000 mg/kg, CK-H), CK medium-dose group (500 mg/kg, CK-M), CK low-dose group (250 mg/kg, CK-L) and methotrexate-positive drug group (MTX); the drug was administered continuously for 28 days. Body weight changes, joint swelling, arthritis index, bone density, ankle lesions, immune organ index, splenic lesions and inflammatory factor expression were used to evaluate the in vivo anti-RA activity of the extract. RESULTS: The findings of in vitro experiments showed that 10% CK-containing serum decreased the expression level of Bcl-2, increased the expression levels of Bax and Cleaved Caspase-3 in synovial cells, and prevented TNF-α induced aberrant proliferation and apoptotic antagonism in HFLS-RA cells. According to in vivo studies, CK extract at doses above 250 mg/kg was effective in controlling the levels of inflammatory factors, lowering the arthritis index, and improving foot swelling in CIA rats. When administered at doses up to 1000 mg/kg, CK extract significantly improved synovial lesions, increased bone density, and decreased abnormally elevated immune organ index in CIA rats. CONCLUSIONS: CK has significant anti-RA activity, and its anti-RA mechanism of action may be related to the regulation of the expression levels of apoptosis related proteins and the promotion of apoptosis in synovial cells.

Agrimoniin is a dual inhibitor of AKT and ERK pathways that inhibit pancreatic cancer cell proliferation.

Molecular-targeted therapy has shown its effectiveness in pancreatic cancer, while single-targeted drug often cannot provide long-term benefit because of drug resistance. Fortunately, multitarget combination therapy can reverse drug resistance and achieve better efficacy. The typical treatment characteristics of traditional Chinese medicine monomer on tumor are multiple targets, with small side effects, low toxicity, and so forth. Agrimoniin has been reported to be effective on some cancers, while the mechanism still needs to be clarified. In this study, we used 5-ethynyl-2'-deoxyuridine, cell counting kit-8, flow cytometry, and western blot experiments to confirm that agrimoniin can significantly inhibit the proliferation of pancreatic cancer cell PANC-1 by inducing apoptosis and cell cycle arrest. In addition, by using SC79, LY294002 (the agonist or inhibitor of AKT pathway), and U0126 (the inhibitor of ERK pathway), we found that agrimoniin inhibited cell proliferation by simultaneously inhibiting AKT and ERK pathways. Moreover, agrimoniin could significantly increase the inhibitory effect of LY294002 and U0126 on pancreatic cancer cells. Meanwhile, in vivo experiments also supported the above results. In general, agrimoniin is a double-target inhibitor of AKT and ERK pathways in pancreatic cancer cells; it is expected to be used as a resistance reversal agent of targeted drugs or a synergistic drug of the inhibitor of AKT pathway or ERK pathway.

Efficient decolorization of oligosaccharides in ginseng (Panax ginseng) residue using ultrasound-assisted macroporous resin.

An efficient decolorization method for ginseng residue oligosaccharides (GROs) using ultrasound-assisted D392 macroporous resin was developed. The decolorization effects and color differences of activated carbon adsorption, hydrogen peroxide oxidation, and resin adsorption were evaluated. The optimal conditions of the three decolorization methods for static, dynamic, ultrasound-assisted resin adsorption were compared. The results showed that ultrasound-assisted decolorization had the best decolorization effect of greatly decreasing the decolorization time to 80 min. Color difference analysis revealed the process of pigment removal during GRO decolorization. The UV-visible full-wavelength scan showed that most pigments were removed after decolorization. The characterizations by the Fourier-transform infrared spectroscopy and X-ray diffraction analysis showed that the chemical structure and crystallinity of the GROs did not change upon decolorization. In addition, the molecular weight distribution did not change significantly. This research contributes to further exploration of the structures and functions of GROs.

Analysis of the cluster efficacy and prescription characteristics of traditional Chinese medicine intervention for non-small cell lung cancer based on a clustering algorithm.

BACKGROUND: In recent years, malignant tumors have gradually become one of the main causes of death for Chinese residents, of which lung cancer ranks first in both the incidence and mortality in China. OBJECTIVE: To mine the text of traditional Chinese medicine (TCM) clinical medical cases after data cleaning, analyze it, and study the experience of TCM doctors in treating non-small cell lung cancer (NSCLC). METHODS: The applied approach was based on the data mining methods of decentralized and hierarchical system clustering of data from a drug and prescription database. This study involved 215 patients, 287 cases, and 147 types of clinical drugs. RESULTS: The data analysis of the clinical treatment of NSCLC in TCM showed that Erchen Decoction was the main method for the treatment of non-small cell lung cancer in clinical treatment of non-small cell lung cancer. Junjian recipes were close to each other, with Banzhilian, Lobelia, Shanci Mushroom, Hedyotis diffusa to anticancer and detoxify. CONCLUSION: This study analyzed the core TCM prescription for NSCLC by collecting the empirical essence and characteristics of specific medications. It has some guiding scientific significance for the clinical treatment of lung cancer.

Betulinic acid, a major therapeutic triterpene of Celastrus orbiculatus Thunb., acts as a chemosensitizer of gemcitabine by promoting Chk1 degradation.

ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb., also called as oriental bittersweet vine or climbing spindle berry, a traditional Chinese herbal medicine has been used to treat a spectrum of painful and inflammatory diseases for centuries. Explored for their unique medicinal properties, C.orbiculatus offers additional therapeutic effects on cancerous diseases. The effect of single-agent gemcitabine on survival has not long been encouraging, combination therapies provide patients multiple chances of benefit for improved clinical response. AIMS OF THIS STUDY: This study aims at expounding the chemopotentiating effects and underlying mechanisms of betulinic acid, a primary therapeutic triterpene of C. orbiculatus in combination with gemcitabine chemotherapy. MATERIALS AND METHODS: The preparation of betulinic acid was optimized using ultrasonic-assisted extraction method. Gemcitabine-resistant cell model was established by induction of the cytidine deaminase. MTT, colony formation, EdU incorporation and Annexin V/PI staining assays were used to evaluate cytotoxicity, cell proliferation and apoptosis in BxPC-3 pancreatic cancer cell line and H1299 non-small cell lung carcinoma cell line. Comet assay, metaphase chromosome spread and γH2AX immunostaining were applied for DNA damage assessment. Western blot and co-immunoprecipitation was used to detect the phosphorylation and ubiquitination of Chk1. Mode of action of gemcitabine in combination with betulinic acid was further captured in BxPC-3-derived mouse xenograft model. RESULTS: We noticed that the extraction method had an impact on the thermal stability of C. orbiculatus. Ultrasound-assisted extraction at room temperature in shorter processing time could maximize the overall yields and biological activities of C. orbiculatus. The major constituent was identified as betulinic acid, and the pentacyclic triterpene represented the prominent anticancer activity of C. orbiculatus. Forced expression of cytidine deaminase conferred acquired resistance to gemcitabine, while betulinic acid displayed equivalent cytotoxicity toward gemcitabine-resistant and sensitive cells. A combination therapy of gemcitabine with betulinic acid produced synergistic pharmacologic interaction on cell viability, apoptosis and DNA double-strand breaks. Moreover, betulinic acid abrogated gemcitabine-triggered Chk1 activation by destabilizing Chk1 loading via proteasomal degradation. The combination of gemcitabine and betulinic acid significantly retarded BxPC-3 tumor growth in vivo compared to single-agent gemcitabine treatment alone, accompanied with reduced Chk1 expression. CONCLUSIONS: These data provide evidence that betulinic acid is a potential candidate for chemosensitization as a naturally occurring Chk1 inhibitor and warrants further preclinical evaluation.

Structure and properties of Pickering emulsions stabilized solely with novel buckwheat protein colloidal particles.

In this paper, buckwheat protein colloidal particles (BPCPs) were prepared by heat treatment to stabilize oil-water interface. The results of particle size, surface hydrophobicity and wettability indicated that the prepared BPCPs could be used as novel Pickering emulsifier. The effects of BPCPs concentration, ionic strength and heat treatment on the structure and properties of Pickering emulsions were explored. The microstructure results showed that BPCPs could tightly coated on the surface of oil droplets to form a tight interfacial film, confirming that BPCPs could be used as an effective Pickering-like stabilizer. With the increase of BPCPs concentration, the droplet size of the Pickering emulsion gradually decreased, and the viscoelasticity and storage stability of the emulsion were effectively improved. Different from the effect of ionic strength, heat treatment was beneficial to increasing the viscoelasticity of BPCPs-stabilized Pickering emulsion. The Pickering emulsions exhibited certain flocculation at different temperatures and ionic strengths, while still maintained good solid-like behavior. These results suggest that the structure and properties of BPCPs-stabilized Pickering emulsion could be regulated by changing the ionic strength and temperature.

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Screening of quantitative preparation quality markers of Zhibao Sanbian Wan / 药学学报

On the basis of the qualitative preparation quality markers of Zhibao Sanbian Wan (ZBSBW), we screened out the quantitative markers and evaluated the content consistency of ZBSBW. A method capable of simultaneously determining 34 compounds in ZBSBW was established based on HPLC-MS/MS, and 16 batches of ZBSBW were simultaneously analyzed by this method. Furthermore, we explored a general strategy for analyzing the component migration in preparation, plasma, brain tissue and cerebrospinal fluid. The methodological investigation was confirmed by linear range, recovery (85.10%-105.07%), precision (RSD: 1.37%-4.58%), stability, and repeatability (3.00%-12.45%), the established method was suitable for the detection and quantification of the compounds in ZBSBW. The contents of compounds in ZBSBW were all lower than 1 mg·g-1, and the contents and daily dose of nystose were the highest, followed by echinacoside, paeoniflorin, osthole and paeonol. The results of systematic clustering showed that the contents were consistent for ordinary preparations of ZBSBW. The principal component analysis showed that the components of berberine, ginsenoside Re, ginsenoside Rg1, pinoresinol diglucoside and tenuifolin had large variation, which contributed significantly to the grouping. The contents of echinacoside, verbascoside, polygalaxanthone Ⅲ, β-ecdysterone, osthole, alisol B 23-acetate, liquiritin and glycyrrhizic acid were stable from batch to batch. The animal experiment results showed that osthole, paeonol and liquiritin in ZBSBW could be absorbed into the blood and enter the brain tissue by passing through the blood-brain barrier. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2020B071). The above compounds contributed the quantitative preparation quality markers of ZBSBW. In conclusion, the HPLC-MS/MS method established in this study was sensitive, accurate and rapid, and could be used for simultaneous quantification of 34 compounds and content consistency evaluation of multiple batches of preparations in ZBSBW. The result provided a methodological basis for the screening of quantitative preparation quality markers and material basis research of ZBSBW.

White Matter Damage in Major Depressive Disorder and TCM Treatment： A Review / 中国实验方剂学杂志

At present， major depressive disorder （MDD） is highly prevalent with advanced neurological disorders as the main pathological manifestations. As the physiological function bearer of higher neural activity， gray matter has become the focus of MDD treatment. However， recent research has shown that white matter and gray matter are independent of each other in the central nervous system （CNS）， and their functions are integrated and linked. In addition to gray matter damage， white matter damage is also the core driving event of disease progression and determines the outcome of MDD. At the treatment level， the current drug treatment of MDD mainly focuses on gray matter repair， while ignoring the importance of white matter integrity for the treatment of the disease， which has become the weakness of the current treatment of MDD. Traditional Chinese medicine （TCM） has good application potential in white matter repair. This paper elaborated on the following three aspects. ① The roles of white matter damage in the occurrence and development of MDD were summarized. ② The key link of white matter repair in MDD was elaborated with microglia microenvironment regulation as the entry point. ③ The application value of TCM in white matter repair in MDD was analyzed. This review aims to highlight the importance of white matter integrity in the treatment of MDD and is expected to expand the understanding dimension of the activity of related Chinese medicines in MDD from the perspective of white matter repair and analyze its potential application value.

Yi Shen Juan Bi Pill alleviates bone destruction in inflammatory arthritis under postmenopausal conditions by regulating ephrinB2 signaling.

Yi Shen Juan Bi Pill (YSJB) is a traditional Chinese medicine (TCM) formulation that has a therapeutic effect upon rheumatoid arthritis (RA), but how YSJB affects bone destruction in arthritis under postmenopausal conditions is not known. We evaluated the therapeutic role of YSJB in bone destruction in postmenopausal arthritis, We used collagen-induced arthritis (CIA) rats who had been ovariectomized (OVX) as models and explored the possible mechanism from the synovium and bone marrow (BM). Arthritis was generated after ovariectomy or sham surgery for 12 weeks. After 14 days of primary immunization, rats were administered YSJB or estradiol valerate (EV) for 28 days. YSJB could prevent bone destruction in the inflamed joints of rats in the OVX + CIA group. CIA promoted osteoclast differentiation significantly in the synovial membrane according to tartrate resistant acid phosphatase (TRACP) staining, and OVX tended to aggravate the inflammatory reaction of CIA rats according to hematoxylin-and-eosin staining. Immunohistochemistry revealed that the synovium did not have significant changes in erythropoietin-producing hepatocellular interactor (ephrin)B2 or erythropoietin-producing hepatocellular (eph) B4 expression after YSJB treatment, but YSJB treatment reduced nuclear factor of activated T cells (NFATc)1 expression. The BM of rats in the OVX + CIA exhibited remarkable increases in the number of osteoclasts and NFATc1 expression, as well as significantly reduced expression of ephrinB2 and ephB4 compared with the CIA group and sham group. YSJB treatment reduced NFATc1 expression significantly but also increased ephrinB2 expression in the BM markedly. These data suggest that YSJB exhibit a bone-protective effect, it may be a promising therapeutic strategy for alleviating bone destruction in arthritis under postmenopausal conditions, and one of the mechanisms is associated with the modulation of ephrinB2 signaling.

Beware of the Potential Risks for Polygoni Multiflori Caulis-Induced Liver Injury.

Background: Reynoutria multiflora (Thunb.) Moldenke (PM) is a widely-used medicinal plant in China, whose root and stem are included in the Chinese Pharmacopoeia as Polygoni Multiflori Radix (RPM), Polygoni Multiflori Radix Preparata (PMP), and Polygoni Multiflori Caulis (PMC). The hepatotoxicity of RPM and PMP is concerned by the public, while the risk of PMC is ignored. Purpose: Here, we investigate the potential risks for PMC-induced liver injury from clinical, chemical, and animal features. Study design: First, we analyzed the 12-month usage of RPM, PMP, and PMC in Longhua Hospital. Second, we determined the contents of gallic acid, cis-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (cis-SG), trans-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (trans-SG), emodin-8-O-ß-D-glucoside (EG), physcion-8-O-ß-D-glucoside (PG), emodin, and physcion in the water extracts from 15 batches of RPM, PMP, and PMC. Third, we probed the hepatotoxic effect of RPM, PMP, and PMC in mice and explored the mechanism of cis-SG and trans-SG causing the liver injury at the dosages based on our results from the first and second parts. Results: PMC had nearly five times the amount of usage in both outpatient prescriptions and inpatient orders than RPM and PMP. Overall, 68% dosage of PMC was 30 g. The contents of cis-SG, trans-SG, and emodin in PMC water extracts were significantly lower than those in RPM and PMP water extracts. PMC induced milder idiosyncratic liver injury for its lower content of cis-SG and trans-SG than its root counterparts. Conclusion: The potential risks for PMC-induced liver injury should be fully aware of.

Fingerprinting and Determination of Hepatotoxic Constituents in Polygoni Multiflori Radix Praeparata of Different Producing Places by HPLC.

Polygoni Multiflori Radix Praeparata (PMRP) is used as Chinese herbal medicine with long history. However, reports about PMRP hepatotoxicity have increased recently, and producing area might be one reason. This article aims to figure out the relationship between producing area and hepatotoxic ingredients in PMRP. HPLC fingerprint for PMRP was established and the contents of gallic acid, trans-stilbene glycoside (TSG), emodin-8-O-ß-D-glucoside (EG), emodin and physcion were determined. Clustering heatmap was implemented by TCMNPAS software，and principal component analysis was implemented by SPSS and SIMCA-P software. Hepatotoxic constituents' contents of PMRP from separate producing area were different. PMRP from Guangxi had the highest content of gallic acid, TSG, EG, emodin and physcion, followed by Hubei, Guangdong, Guizhou, Yunnan. PMRP from Henan had the lowest contents of hepatotoxic components. Hepatotoxic components' contents of PMRP in southern were higher than central China. This study carried out a preliminary qualitative and quantitative investigation on the PMRP from different producing places, which provided a basis for safe medication of PMRP.

The analgesic activities of total alkaloids of the ethnic medicine Cynanchum komarovii Al. Iljinski.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii Al. Iljinski is a ethnomedicinal herb and this ethno-medicine is used mainly to treat arthritis, toothache, reducing phlegm, relieving cough. Total alkaloids of Cynanchum komarovii Al. Iljinski (TACKI) is the main active compound of Cynanchum komarovii Al. Iljinski. Previous investigations have revealed that TACKI can significantly inhibit rat foot swelling caused by carrageenan; it has a significant inhibitory effect on granulation tissue proliferation. Pharmacology study showed that Cynanchum komarovii Al. Iljinski has analgesia, anti-inflammatory, antibacterial, anti-tumor, relieving cough and relieving asthma. However, there is no any investigation on the mechanism of analgesia and anti-inflammation. AIM OF THE STUDY: To clarify the analgesic effect and material basis of Cynanchum komarovii Al. Iljinski, determine the analgesic effect of TACKI, and provide experimental data support for its traditional application in the treatment of various pains. MATERIALS AND METHODS: TACKI were prepared by the traditional acid extraction and alkaline precipitation method, and TACKI was analyzed through classic animal models of acute antinociceptive animal models and chronic antinociceptive. Evaluation of analgesic effects, and preliminary discussion of the mechanism of its analgesic effects were performed in this work. RESULTS: Acute toxicity experiments showed that the LD50 of TACKI mice was 2960.88 mg/kg, and symptoms of poisoning appeared. Patholog of liver and kidney studies have shown that TACKI reduces eosinophils and increases basophils in kidney glomeruli. In the study of analgesic effects, TACKI had analgesic activity through the PWL, formalin test, and acetic acid writhing test. In the chronic inflammatory antinociceptive study, the latency of the withdrawal reflex in the TACKI group was prolonged, and the mechanical withdrawal reflex threshold was significantly increased. The protein expression of NMDA, GFAP and Iba-1 in rat brain tissue can be reduced significantly byTACKI. Meanwhile, the content of TNF-α and IL-6 in rat brain tissue is reduced. CONCLUSION: TACKI has a significant analgesic activities. It may be related to inhibiting the activation of astrocytes and reducing the content of inflammatory mediators.

Mechanism of lung and intestine combination therapy in treatment of acute lung injury by inhibiting inflammatory response based on NF-κB/NLRP3 signaling pathway and alveolar macrophage activation / 中国中药杂志

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.