An alkaloid from Menispermum dauricum, dauricine mediates Ca2+ influx and inhibits NF-κB pathway to protect chondrocytes from IL-1ß-induced inflammation and catabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Dauricine (DA) is a natural plant-derived alkaloid extracted from Menispermum dauricum. Menispermum dauricum has been used in traditional Chinese medicine as a classic remedy for rheumatoid arthropathy and is believed to be effective in alleviating swelling and pain in the limbs. AIM OF THE STUDY: Osteoarthritis (OA) is a classic degenerative disease involving chondrocyte death, and there is still a lack of effective therapeutic agents that can reverse the progression of the disease. Here we explored the therapeutic effects of DA against OA and further explored the mechanism. MATERIALS AND METHODS: The effect of DA on cell viability was assessed by CCK-8. IL-1ß-treated mouse chondrocytes were used as an in vitro model of OA, and apoptosis was detected by flow cytometry. QRT-PCR, western blotting, cell staining, and immunofluorescence were used to detect relevant inflammatory factors and cartilage-specific expression. RNA sequencing was used to identify pertinent signaling pathways. The therapeutic effect of DA was verified by micro-CT, histological analysis and immunohistochemical analysis in a mouse OA model. RESULTS: DA demonstrated a high safety profile on chondrocytes, significantly reversing the inflammatory response induced by IL-1ß, and promoting factors associated with cartilage regeneration. Moreover, DA exhibited a significant protective effect on the knee joints of mice undergoing ACLT-DMM, effectively preventing cartilage degeneration and subchondral bone tissue destruction. These positive therapeutic effects were achieved through the modulation of the NF-κB pathway and the Ca2+ signaling pathway by DA. CONCLUSION: Being derived from a traditional herb, DA exhibits remarkable therapeutic potential and safety in OA treatment, presenting a promising option for patients dealing with osteoarthritis.

Polycyclic aromatic hydrocarbons in the Chinese diet: contamination characteristics, indicator screening, and health risk assessment.

Polycyclic aromatics hydrocarbons (PAHs) are ubiquitous in foods and environment and possess carcinogenic and mutagenic potential. Foods are the main source of exposure to PAHs in the general population. In this study, we determined the concentrations of 16 European Union priority PAHs in 1,564 foodstuffs acquired from nine provinces and commonly consumed by the Chinese population. The most predominant PAH was chrysene (16.7%), followed by benz[a]anthracene (12.4%) and benzo[b]fluoranthene (11.7%). Edible vegetable oils (17.89 µg/kg) and fruits (1.97 µg/kg) had the highest and lowest concentrations of total PAHs, respectively. Suitable indicators of PAH contamination in foods were assessed based on the occurrence of other PAHs in samples negative for benzo[a]pyrene and the correlation for the PAHs and their combinations. According to our results, PAH4 was a suitable indicator, better than PAH8 and benzo[a]pyrene alone. PAH exposure in the Chinese population was estimated by combining contamination data with national individual food consumption data, based on the middle bound approach. The overall average dietary exposures for BaP and PAH4 were 3.08 and 17.61 ng/kg bw/day, respectively. The major contributors to the total dietary exposure of PAHs were cereals (39%), edible vegetable oils (28%), and vegetables (20%). We used the margin of exposure (MOE) approach to assess health risk for consumers. MOEs of the mean estimated dietary exposures were >10,000, indicating a low concern for the health of the general population and of consumers of smoked, grilled, or barbecued foods. For high consumers and children, the MOEs were <10,000, indicating potential concerns.

Panaxydol Derived from Panax notoginseng Promotes Nerve Regeneration after Sciatic Nerve Transection in Rats.

BACKGROUND: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. METHODS: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. RESULTS: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. CONCLUSIONS: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.

Quantitative probabilistic assessment of caffeine intake from tea in Chinese adult consumers based on nationwide caffeine content determination and tea consumption survey.

Caffeine has known effects on the central nervous and cardiovascular systems. An intake up to 400 mg/day does not give rise to health concerns. Tea, a major source of caffeine, is highly consumed in China. However, the potential health risk of caffeine from tea has not been well evaluated. The present study assessed caffeine intake levels from tea for Chinese adult consumers. We collected 1,398 samples of green, black, dark, jasmine, oolong, white, and yellow tea from 17 provinces. The caffeine content was determined by HPLC. The average contents were 27 (oolong tea) - 43 (yellow tea) mg/g. The leaching rate of caffeine into the water was about 100%. Tea consumption data were from the National Beverage Consumption Survey 2013-2014. Monte Carlo simulations were applied to estimate the distribution of caffeine intake. The average caffeine intake from tea was 180 mg/day of all consumers. Green, dark, and black tea were the primary sources. Males (197 mg/day) consumed more caffeine than females (136 mg/day) on average, but females older than 71 years had the highest intake level (259 mg/day) among all subgroups. Over 90% of Chinese adult tea drinkers have caffeine intake under 400 mg/day.

Analysis of furan and its major furan derivatives in coffee products on the Chinese market using HS-GC-MS and the estimated exposure of the Chinese population.

The current study analysed concentrations of furan and its derivatives in coffee products commercially available in China based on an improved headspace gas chromatography-mass spectrometry (HS-GC-MS) method and estimated health risks. A total of 101 samples of coffee products on the Chinese market was analysed. Furan (98%, ND-6569 µg/kg) and 2-methylfuran (100%, 2-29639 µg/kg) were the compounds with the highest concentrations and detection rates in coffee products. The mean dietary exposure of Chinese consumers to furan and the sum of furan, 2-methylfuran and 3-methylfuran in coffee products was 0.09 and 0.46 µg/kg bw/day, respectively. For the neoplastic effects of furan, the margin of exposure (MOE) was 14,556 for the mean dietary exposure of consumers. For the non-neoplastic effects of furan, MOEs were 711 and 139 for furan and the sum of furan, 2-methylfuran and 3-methylfuran, respectively. Overall, a health concern is indicated for coffee consumers with MOEs below 10000.

Traditional Chinese Medicine Text Similarity Calculation Model Based on the Bidirectional Temporal Siamese Network.

The text similarity calculation plays a crucial role as the core work of artificial intelligence commercial applications such as traditional Chinese medicine (TCM) auxiliary diagnosis, intelligent question and answer, and prescription recommendation. However, TCM texts have problems such as short sentence expression, inaccurate word segmentation, strong semantic relevance, high feature dimension, and sparseness. This study comprehensively considers the temporal information of sentence context and proposes a TCM text similarity calculation model based on the bidirectional temporal Siamese network (BTSN). We used the enhanced representation through knowledge integration (ERNIE) pretrained language model to train character vectors instead of word vectors and solved the problem of inaccurate word segmentation in TCM. In the Siamese network, the traditional fully connected neural network was replaced by a deep bidirectional long short-term memory (BLSTM) to capture the contextual semantics of the current word information. The improved similarity BLSTM was used to map the sentence that is to be tested into two sets of low-dimensional numerical vectors. Then, we performed similarity calculation training. Experiments on the two datasets of financial and TCM show that the performance of the BTSN model in this study was better than that of other similarity calculation models. When the number of layers of the BLSTM reached 6 layers, the accuracy of the model was the highest. This verifies that the text similarity calculation model proposed in this study has high engineering value.

Evaluation on Antidiabetic Properties of Medicinal Plants from Myanmar.

OBJECTIVES: To explore the effective and safe medicines for treating diabetes. METHODS: Hydroalcoholic extracts of 130 medicinal plants belonging to 66 families were evaluated using porcine pancreatic lipase (PPL) inhibition and glucose uptake methods together with a literature review. RESULTS: The extracts of 22 species showed the PPL inhibition activity; 18 extracts of 15 species stimulated glucose uptake in 3T3-L1 adipocytes. Among them, Mansonia gagei J.R. Drumm., Mesua ferrea L., and Centella asiatica (L.) Urb. exhibited both activities. The extracts of Caladium lindenii (André) Madison rhizomes and Azadirachta indica A. Juss. leaves presented the utmost lipase inhibitory activity with IC50 of 6.86 ± 0.25 and 11.46 ± 0.06 µg/mL, respectively. The extracts of Coptis teeta Wall. rhizomes and Croton tiglium L. seeds stimulated the maximum glucose uptake. Ten species are reported to have antidiabetic activity for the first time. Flavonoids and triterpenoids are the dominant antidiabetic compounds in selected medicinal plants from Myanmar. CONCLUSIONS: P. zeylanica, L. cubeba, H. crenulate, M. gagei, C. teeta, and M. ferrea are worthy to advance further study according to their strong antidiabetic activities and limited research on effects in in vivo animal studies, unclear chemical constitutes, and safety.

Chinese herbal medicine Feiyanning cooperates with cisplatin to enhance cytotoxicity to non-small-cell lung cancer by inhibiting protective autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Feiyanning (FYN), the Chinese herbal medicine (CHM), has been used to manage non-small cell lung cancer (NSCLC) for the past 23 years. Chemotherapeutic drugs can induce autophagy in cancer cells to protect themselves from death. However, FYN can inhibit the protective autophagy in cancer cells. We investigated the biological mechanisms on the synergistic effects of FYN combined with chemotherapy in lung cancer cells. MATERIALS AND METHODS: We analyzed the effective chemical components for the quality control of FYN using the UPLC-Q-TOF-MS.The cell proliferation ability was detected by the cell counting kit-8 (CCK-8) and colony formation. The cell apoptosis was determined with Flow cytometry. Expression of important differential proteins were detected by western blot. Autophagy structure was observed by TEM (Tansmission electron microscopy). Tandem mCherry-EGFP-LC3B immunofluorescence was used to measure autophagic flux. RESULTS: Both FYN and cisplatin significantly induced apoptosis and inhibited cell proliferation in A549 cells. FYN reduced cell viability and increased apoptotic cell populations less effectively than cisplatin. FYN cooperated with cisplatin suppressed the cell viability, colony formation, as well as increased the cell apoptosis rate, and the expression of cleaved caspase-3 and PARP. FYN inhibited autophagy in A549 cells, which characterized by the decrease of autophagosome formation, lysosomal fusion, LC3B-II accumulation and SQSTM1 degradation, down-regulation of ATG5 and ATG7. Protective autophagy in A549 cells was induced by cisplatin. Suppression of the autophagic response using chloroquine (CQ) which is autophagy inhibitor improved the ability of cisplatin to kill cancer cells, as did FYN combined with cisplatin. CONCLUSION: In summary, we revealed that the synergistic mechanism of FYN and cisplatin is that FYN inhibited the protective autophagy induced by cisplatin in A549 cells.

Cinobufagin-Loaded and Folic Acid-Modified Polydopamine Nanomedicine Combined With Photothermal Therapy for the Treatment of Lung Cancer.

Cinobufagin is used as a traditional Chinese medicine for cancer therapy. However, it has some disadvantages, such as poor water solubility, short circulating half-life, and low bioavailability. In the present study, a targeted delivery and smart responsive polydopamine (PDA)-based nanomedicine for delivering cinobufagin was rationally designed to improve the anticancer efficacy of the compound for the treatment of lung cancer. The modification of the nanomedicine using folic acid first mediated tumor targeting via the interaction between folic acid and its receptors on tumor cells. After lysosomes escape, the PDA nanomedicine was triggered by the low pH and released its cargo into the tumor microenvironment. The nanomedicine had a better therapeutic effect against lung cancer when used in combination with photothermal therapy. Compared with other nanomedicines used with photothermal therapy, this nanocarrier was not only sensitive to biologically low pH levels for on-demand drug release, but was also biodegradable, breaking down into biocompatible terminal products. Therefore, the proposed drug delivery system with targeted delivery and smart release demonstrated potential as a multifunctional nanoplatform that can enhance the bioavailability and reduce the side effects of chemotherapeutic agents.

Poisonous delicacy: Market-oriented surveys of the consumption of Rhododendron flowers in Yunnan, China.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants from the family Ericaceae, and in particular those in the genus Rhododendron are frequently reported to contain grayanotoxins. Plant products such as honey and herbal medicines made from these plants occasionally contain grayanotoxins, and in turn may lead to intoxication. The balance between the benefits and risk of poisoning from Rhododendrons is of concerns. This study explores the ethnobotanical knowledge of the people in Yunnan, China as regards the consumption of Rhododendron flowers, and gives special focus to their assessment of the benefit-risk balance. MATERIALS AND METHODS: An ethnobotanical survey was conducted across 14 county-level local markets in north and central Yunnan province, during which a total of 82 stalls selling Rhododendron flowers were visited and 204 people were interviewed. Voucher specimens were obtained under the guidance of collectors, and details about local practices and knowledge were recorded using semi-structured interviews and participatory observations. RESULTS: The consumption of the corollas of Rhododendron decorum Franch. Flowers (RDf) or Rhododendron pachypodum Balf. f. & W.W. Sm. Flowers (RPf) as a seasonal delicacy is a long-standing tradition in the study area. RDf are widely consumed in northwest and northeast Yunnan, while RPf are more prevalent in the central regions of Yunnan, and there is a high consistency in the knowledge of the process for detoxification or palatability for each species. The main reasons for eating the flowers were listed as health benefits (mostly clear heat), wild collected, tradition and good flavor. All RPf consumers stated that the corolla from this species is not toxic, while 67.4% of the RDf consumers claim that the corolla from RDf is toxic. We compared the two species and analyzed their process intensities, poisoning cases and cautions, market trade forms and existing toxicity studies, which agreed well and consistently that the corolla of RDf deserve more toxicity attention than RPf. CONCLUSION: Our study provides a window to look into the ways, beyond honey and herbal medicine, by which Rhododendron species have influenced human wellbeing. The local culture can justify eating Rhododendron flowers, and meanwhile, has developed a series of skills to avoid the side effects of eating them, and therefore the study also provides a good case to answer more general questions about the rationality of eating any plant products by assessing the trade-off between benefits and side effects.

Dietary exposure of general Chinese population to fatty acid esters of 3-monochloropropane-1, 2-diol (3-MCPD) from edible oils and oil-containing foods.

Edible oils and oil-containing foods have been regarded as the main source of 3-monochloropropane-1, 2-diol (3-MCPD) esters. A total of 3,847 individual food samples were collected in China to carry out 3-MCPD fatty acid esters analysis. The samples comprising edible oils, fried foods and bakery foods from 31 Chinese provinces, municipalities and autonomous regions were obtained from the national food contaminant information system during 2015-2017. The dietary exposure and potential risks associated with the consumption of 3-MPCD esters from edible oils and oil-containing foods were estimated using a semi-probabilistic assessment model. Concentrations of 3-MCPD fatty acid esters in food samples were detected by gas chromatography-mass spectrometry (GC-MS). The mean levels of 3-MCPD fatty acid esters in edible oils, fried foods and bakery foods were 0.862, 0.249 and 0.145 mg/kg, respectively. The range of mean dietary intakes of 3-MCPD esters in different subpopulation groups (classified by gender and age) was from 0.586 to 1.539 µg/kg bw/day, which were all lower than 2 µg/kg bw/day - the tolerable daily intake (TDI) established by the European Food Safety Authority (EFSA). The range of dietary intake of 3-MCPD esters in high consumers (95th percentile) in each group was from 1.511 to 4.027 µg/kg bw/day, which accounted for 75.6% to 201.4% of the TDI. The 3-MCPD esters exposure level of 3.5% of the total Chinese population exceeded the TDI. The findings indicate that the potential health risks caused by dietary 3-MCPD esters from edible oils and oil-containing foods were of low concern for most of the Chinese population. However, the exposure risk of the consumers with excessive edible oil consumption calls for attention.

The secret of health in daily cuisine: typical healthy vegetables in local markets in central Myanmar.

BACKGROUND: Central Myanmar is located in the Indo-Burma biodiversity hotspot, and the Bamar people are the main ethnic group, which settled there over 1000 years ago. Despite being the core region of the country, central Myanmar has been ignored in previous ethnobotanical studies. Local healthy foods and knowledge are regarded as treasures for resource development and pharmaceutical drug discovery, and market surveys are a good strategy in ethnobotanical research. Thus, we collected and documented typical vegetables and local knowledge in local markets and then analysed the diversity and local knowledge of these vegetables. MATERIALS AND METHODS: Observations and interviews were used in the field study, and 10 markets and fairs were selected in central Myanmar. A total of 277 vegetable stalls or shops were visited. We compared the local knowledge we collected with selected important and typical herbal books on traditional Myanmar medicine. Quantitative analysis, including frequency of citation (FC), relative frequency of citation (RFC) and use value (UV), was used to assess the diversity and local knowledge of these vegetables. RESULTS: A total of 132 plant taxa from 47 botanical families and 116 genera were collected. Most (106 taxa, 80.3%) of these vegetables were cited by the informants as functional foods that had health benefits, while others were regarded as merely "good for health". The main health function of the vegetables was treating digestive problems. Sixty-four species were recorded in selected herbal books on traditional Myanmar medicine, and forty-seven taxa were not recorded in these books but were nonetheless used as healthy vegetables by local people. Twenty-eight species of vegetables were collected from wild places. CONCLUSION: The diversity and local knowledge of healthy vegetables in central Myanmar were rich. Nevertheless, the diversity of wild vegetables was seemingly relatively low. The possible reason was that we counted only the vegetables that were from entirely wild sources as "wild vegetables". The most frequently cited vegetables were commonly cultivated species, which reflects the fact that plants cultivated on a large scale comprise the major source of vegetables. Some lesser known vegetables could reflect the unique food culture of local people, but most of these were cited only a few times by the interviewees, which caused low UV and RFC rankings for them in the league table. In addition, future research should pay more attention to the food safety of these vegetables.

A billion cups: The diversity, traditional uses, safety issues and potential of Chinese herbal teas.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal teas have long been consumed by Chinese people for preventive and/or therapeutic healthcare. Although herbal teas are widely consumed by many cultural groups in different regions of China, no thorough review has been undertaken to assess the diversity of the country's herbal tea usage. This literature review, complemented by a quantitative survey in an important tea market in Kunming, begins to fill this knowledge gap. AIMS OF THE STUDY: The study aims to summarize the current knowledge of plant species used as herbal teas by different cultural groups in different regions of China, with a focus on the teas' perceived traditional healthcare functions, related phytochemical/pharmaceutical research, and safety issues. MATERIALS AND METHODS: The study involved a comprehensive literature review and a market survey. The literature review was based on published ethnobotanical studies of herbal teas in China. We searched the Web of Science™, ELSEVIER, the China National Knowledge Infrastructure (CNKI) and the China Science and Technology Journal Database to locate relevant studies (including journal articles, Masters/PhD dissertations and books) that were published before March 2017. A species list was compiled based on the review and supplemented with information retrieved from the Scifinder database (https://scifinder.cas.org) and the Chinese Pharmacopoeia (2010). A Use Value Index was employed for ranking the most cited species. Based on the 29 most cited species, we discussed the current research status in relation to healthcare benefits and safety concerns of herbal teas in China. To better understand the current status of the herbal tea market in China, we also surveyed 136 tea vendors at the Xiongda Tea Market in Kunming. Information gathered from the survey included the species sold, the sale prices and the form of the herbal tea product. RESULTS: The literature identified 759 plant species used as herbal tea in China and the market survey identified an additional 23 species. Most of the species used were from the Leguminosae, Compositae and Lamiaceae families. Twenty two provinces and fourteen ethnic minority groups have records on the consumption of herbal teas. Southern China uses up to 82% of the total species, and 211 out of 759 species are used by minority groups. Thirty categories of traditional healthcare functions are linked with herbal teas, with clearing away heat, relieving toxicity and suppressing cough being the most important functions. There is phytochemical/pharmaceutical evidence to support the claimed healthcare benefits of some Chinese herbal teas. Although Chinese herbal teas are generally safe to consume, overdoses of some herbal teas and some unapproved mixtures of species may cause health risks. Based on our market survey, the prices of most herbal teas range between 100 and 200 RMB (US$15-30) per kg. CONCLUSIONS: A rich array of herbal tea species with various traditional healthcare functions have long been used in China, and as such there is a huge market potential for Chinese herbal teas. More pharmaceutical/phytochemical research is needed to assess a wide range of perceived healthcare benefits of Chinese herbal teas. Our research highlights the need to study herbal teas through an ethnopharmacological perspective and by employing a holistic approach, which requires greater consideration of traditional knowledge in the pharmacological research design. Product safety and sustainability issues should also be considered, so the traditional applications of herbal teas can be transformed to efficient health boosting functional products.

[Safety and effect of transurethral holmium laser enucleation of the prostate versus bipolar transurethral plasmakinetic prostatectomy for benign prostatic hyperplasia: A meta-analysis].

OBJECTIVE: To evaluate the safety and effect of transurethral holmium laser enucleation of the prostate (HoLEP) in comparison with bipolar transurethral plasmakinetic prostatectomy (TUPKP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: We searched the databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP, and Wangfang Data for controlled clinical trials about HoLEP versus TUPKP in the treatment of BPH published up to April 2016. The studies were screened according to the inclusion and exclusion criteria, the data extracted, and their quality evaluated by 2 reviewers independently, followed by a meta-analysis using the RevMan 5.3 software. RESULTS: A total of 7 studies were included, involving 2031 cases. In comparison with TUPKP, HoLEP showed significantly longer operation time (WMD = 24.61, 95% CI 11.88, 37.34, P lt; 0.001), shorter hospital stay (WMD =－1.91, 95% CI －3.74, －0.07, P = 0.04), shorter bladder irrigation time (WMD = －21.50, 95% CI －34.95, －8.06, P = 0.002), shorter catheter-indwelling time (WMD = －27.60, 95% CI －48.17, －7.03, P = 0.009), less hemoglobin loss (WMD = － 0.42, 95% CI －0.78, －0.07, P = 0.02); lower postvoid residual urine (PVR) at 3 months (WMD = －3.35, 95% CI －4.46, －2.23, P<0.001) and 6 months after surgery (WMD =－1.11, 95% CI －2.18, －0.05, P = 0.04); higher maximum urinary flow rate (Qmax) (WMD = 0.42, 95% CI 0.04, 0.80, P = 0.03) and fewer urinary tract irritation symptoms (OR =0.58, 95% CI 0.41, 0.81, P = 0.002) at 12 months after surgery. No statistically significant differences were found between the two groups in the volume of resected tissue, serum sodium reduction, urethral stricture, erectile dysfunction, retrograde ejaculation, or transient urinary incontinence (P>0.05), or in the improvement of the quality of life (QoL) at 1, 3 and 12 months, International Prostate Symptom Score (IPSS) at 1, 3, 6 and 12 months, Qmax at 1, 3 and 6 months, or International Index of Erectile Function-5 (IIEF-5) at 6 months after surgery (P>0.05). CONCLUSIONS: HoLEP is preferred to TUPKP in clinical application for its advantages of higher Qmax at 12 months after surgery, lower PVR at 3 and 6 months, higher peri-operative safety, faster recovery, and fewer urinary tract irritation symptoms. However, for the quantity and quality limitations of the included publications, our findings are to be further supported by large-sample, multi-center, and high-quality prospective controlled clinical studies.

Baicalin attenuates transforming growth factor-ß1-induced human pulmonary artery smooth muscle cell proliferation and phenotypic switch by inhibiting hypoxia inducible factor-1α and aryl hydrocarbon receptor expression.

OBJECTIVES: Baicalin, a natural flavone, has antithrombotic, antihyperlipidemic and antiinflammortory activity. It can also inhibit cancer cell proliferation and reduce brain cell apoptosis. This study aimed to elucidate the effect of baicalin on the excessive proliferation of human pulmonary arterial smooth muscle cells (HPASMCs) induced by transforming growth factor-ß1 (TGF-ß1) and to investigate the roles of hypoxia inducible factor-1α (HIF-1α) and aryl hydrocarbon receptor (AhR) in mediating this TGF-ß1-induced excessive proliferation of HPASMCs. METHODS: TGF-ß1-induced proliferation of HPASMCs was assayed using the CCK8 method. The cellular phenotype was identified by immunocytochemical staining. Expression of HIF-1α and AhR mRNA was determined by real-time quantitative PCR. KEY FINDINGS: TGF-ß1 promoted significantly HPASMC proliferation (P < 0.05) and induced a phenotypic switch from the contractile to synthetic type. Baicalin inhibited this TGF-ß1-induced phenotypic switch and consequently the excessive growth of HPASMCs in a time-dependent and dose-dependent manner (P < 0.05). Furthermore, baicalin attenuated the abnormal proliferation of HPASMCs through suppression of the HIF-1α and AhR pathways. CONCLUSIONS: Our study shows that baicalin has the potential to be used as a novel drug in the treatment of pulmonary arterial hypertension pathology by antagonizing HIF-1α and AhR expression and subsequently decreasing HPASMC proliferation and the phenotypic switch.

[Chemical constitunents of seeds of Oroxylum indicum].

OBJECTIVE: To study the chemical constituents in the seeds of Oroxylum indicum. METHOD: Twenty compounds were isolated and purified by silica gel, and Sephadex LH-20 column chromatography, and their structures were determined by spectroscopic analysis including NMR and MS. RESULT: Twenty compounds were isolated and identified as oroxin A (1), oroxin B (2), chrysin (3), baicalein (4), quercetin (5), apigenin (6), kaempferol (7), quercetin-3-O-ara-binopyranoside (8), lupeol C9), lup-20 (29)-ene-2alpha,3beta-diol (10), pinosylvin (11), dihydropinosylvin (12), cholest-5-ene-3, 7-diol (13), rengyol (14), isorengyol (15), zarzissine (16), (E) -pinosylvin-3-O-beta-D-glucopyranoside (17), adenosine (18), sitosterol (19) and daucosterol (20). CONCLUSION: Compounds 11-13 and 15-18 were obtained from the genus Oroxylum for the first time, and except compound 18, the remaining 6 compounds were obtained from the family Bignoniaceae for the first time.

[Chemical constituents of Datura stramonium seeds].

OBJECTIVE: To study chemical constituents in the seeds of Datura Stramonium (Solanaceae family). METHOD: Compounds were isolated and purified by silica gel, MCI and Sephadex LH-20 column chromatography, and their structures were determined based on physicochemical constants and spectroscopic analysis including NMR and MS. RESULT: Twelve compounds were isolated and identified from Datura stramonium, they were N-trans-feruloyl tryptamine (1), hyoscyamilactol (2), scopoletin (3), umckalin (4), daturaolone (5), daturadiol (6), N-trans-ferulicacyl- tyramine (7), cleomiscosin A (8), fraxetin (9), scopolamine (10), 1-Acetyl-7-hydrox-beta-carbol-ine (11), 7-hydroxy-beta-carbolinel-propionic acid (12). CONCLUSION: Compound 2, 7, 9 and 12 were obtained from Datura genus for the first time, whereas compound 1, 4, 8 and 11 were obtained from the Solanaceae family for the first time.

Hyperthermic CO2 pneumoperitoneum induces apoptosis in human colon cancer cells through Bax-associated mitochondrial pathway.

Peritoneal carcinomatosis of colorectal cancer is common and associated with poor prognosis, which poses a serious challenge and satisfactory treatments are urgently needed. Hyperthermic CO2 pneumoperitoneum (HT-CO2) is a new strategy. This study was designed to determine the potential of HT-CO2 against colorectal cancer cells. Based on an in vitro HT-CO2 study model, the anti-tumor efficacy of HT-CO2 (42-44 degrees C for 2-4 h) on human colon cancer COLO 205 cells was evaluated and the mechanisms of actions were analyzed. We found that HT-CO2 (43-44 degrees C for 2-4 h) significantly decreased cell viability as determined by WST-8 assay, and the cytotoxicity was attributable to HT-CO2-induced hyperthermia and extracellular acidification. Apoptosis was the major form of cell killing as demonstrated by Annexin-V/PI flow cytometry and morphological analysis (Hoechst/PI fluorescence microscopy and transmission electron microscopy). Further Western blot analysis and flow cytometric analysis of mitochondrial membrane potential showed that Bax-associated mitochondrial apoptotic pathway played critical role in the induction of apoptosis. We conclude that HT-CO2 has significant cytotoxic effect on colon cancer cells through induction of Bax-associated mitochondrial apoptosis, and the cytocidal effect is attributable to HT-CO2-induced hyperthermia and extracellular acidifications. Our data suggest that HT-CO2 may serve as a potential candidate for treating and/or preventing peritoneal carcinomatosis of colorectal cancer and further investigations both in vitro as well as in vivo in animal models are needed.

Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice.

AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT. METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay. RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F = 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (chi2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups. CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.