Publications by authors named "Ying-Jie Chen"

71 Publications

Effect of Guo Qing Yi Tang combined with Western medicine cluster therapy on acute pancreatitis.

Am J Emerg Med 2021 Jul 8;50:66-70. Epub 2021 Jul 8.

Department of Critical Care Medicine, Jinjiang Hospital of Traditional Chinese Medicine, Jinjiang 362200, Fujian province, People's Republic of China.

Background: This study evaluated the effect of Guo Qing Yi Tang (GQYT) combined with Western medicine cluster therapy on acute pancreatitis (AP).

Methods: A total of 138 AP patients were recruited and divided into the observation group (68 patients) and control group (70 patients). The control group was treated with cluster therapy alone, while the observation group was treated with trans-jejunum feeding of GQYT combined with cluster therapy. Blood samples were taken before the treatment and 24 h, 72 h, and 1 week after the treatment. The serum concentrations of Di amine oxidase(DAO), Endotoxin(ET), D-lactic acid, Intestinal trefoil factor(ITF), MFG-E8, TNF-α, IL-1β, IL-6, and IL-8 were determined by using spectrophotometry and enzyme-linked immunosorbent assay. The concentrations of urinary lactulose and mannitol (L/M) were determined by high-performance liquid chromatography, and the urinary L/M value was calculated.

Results: Compared with the control group, the observation group had shorter hospital stay, faster recovery, significantly lower APACHE II score, and higher complete response rate (94.12%) after 1 week of treatment (P < 0.05). Moreover, the indicators related to intestinal mucosal barrier function (DAO, MFG-8, L/M) and inflammatory cytokines (TNF-α, IL-6, IL-8) were significantly reduced in the observation group after 1 week of treatment (P < 0.05).

Conclusion: GQYT combined with cluster therapy for the treatment of AP has definite curative effect and rapid onset, reduces the level of inflammatory factors, and improves intestinal mucosal barrier function and APACHE II score. Thus, it has obvious clinical therapeutic advantages and can be used as a new therapeutic regimen for AP.
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http://dx.doi.org/10.1016/j.ajem.2021.07.004DOI Listing
July 2021

lncRNA RBM5-AS1 promotes cell proliferation and invasion by epigenetically silencing miR-132/212 in hepatocellular carcinoma cells.

Cell Biol Int 2021 May 21. Epub 2021 May 21.

Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China.

Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies worldwide leading to cancer-related death. Long noncoding RNAs (lncRNAs) are a critical modulator affecting HCC progression. Whereas, the pathogenesis of lncRNA RBM5-AS1 in the development of HCC remains unclear. Quantitative RT-PCR or western blot assays were applied to detect the expression of genes and proteins, respectively. The proliferation and metastasis abilities were assessed using Cell counting kit-8 (CCK-8), EdU and transwell assays. RNA immunoprecipitation (RIP) experiment was employed to validate the molecular interactions. RBM5-AS1 is highly expressed in HCC tissues and cell lines, especially in Hep3B and HepG2 cells. RBM5-AS1 knockdown dramatically restrains cell proliferation, invasion and migration of HCC cells. Importantly, RBM5-AS1 acts as an epigenetic regulator to elevate the H3K27me3 level of miR-132/212 promoter regions via recruiting PRC2 (EZH2, SUZ12, EED), and eventually reducing miR-132/212 expressions. The recovery experiments demonstrated that downregulation of miR-132/212 markedly eliminate the antitumor effects mediated by RBM5-AS1 silencing in HCC cells. The data of this work illustrate that RBM5-AS1 acts as an epigenetic regulator to promote the HCC progression by repressing miR-132/212 expressions, which would provide a new insight for understanding the action mechanism of RBM5-AS1 in HCC development.
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http://dx.doi.org/10.1002/cbin.11649DOI Listing
May 2021

The anti-inflammatory effects of an ethanolic extract of the rhizome of Atractylodes lancea, involves Akt/NF-κB signaling pathway inhibition.

J Ethnopharmacol 2021 Sep 13;277:114183. Epub 2021 May 13.

Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Research and Development Center for Natural Health Products, HKBU Institute of Research and Continuing Education, Shenzhen, China. Electronic address:

Ethnopharmacological Relevance: The dried rhizome of Atractylodes lancea (Thumb.) DC. (Compositae) has been prescribed in folk medicine for the management of various inflammatory conditions such as rheumatic diseases, gastritis and hepatitis. However, the molecular mechanisms underlying the beneficial properties of this herb remain elusive.

Aim Of The Study: In this study, we investigated the anti-gastritis activities of Al-EE (an ethanolic extract of the herb) and explored the mechanism of action.

Materials And Methods: An ethanolic extract of the Atractylodes lancea (Thumb.) DC. (Compositae) rhizome, Al-EE, was prepared with ethanol (95%) and quality controlled using HPLC analysis. To determine the in vivo effects of this extract, we utilised a HCl/EtOH-induced gastritis rat model. In vitro assays were carried out using a lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cell model. MTT assays were used to examine cell viability, while Griess assays were carried out to measure nitric oxide (NO) production. Messenger RNA expression was examined by real-time PCR. Prostaglandin E (PGE) production was examined using ELISA assays. To examine protein expression and enzymatic activities, we employed western blot analysis. Nuclear transcription factor (NF)-κB activity was determined by Luciferase reporter assays.

Results: The content of atractylenolide (AT)-1 and AT-2 in Al-EE was 0.45% and 5.07% (w/w), respectively (Supplementary Fig. 1). Al-EE treatment suppressed the production of NO and PGE, reduced the mRNA expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α, while also reducing the protein levels of iNOS and COX-2 in RAW264.7 macrophage cells. Furthermore, Al-EE inhibited the nuclear protein levels of NF-κB (p65) and NF-κB-driven luciferase reporter gene activity in RAW264.7 macrophage cells. Critically, intra-gastric injection of Al-EE (25 mg/kg) attenuated HCl/EtOH-induced gastric damage in SD rats, while the phosphorylation of Akt and IκBα was suppressed by Al-EE in vitro and in vivo.

Conclusion: In summary, Al-EE has significant anti-gastritis effects in vivo and in vitro, which can be associated with the inhibition of the Akt/IκBα/NF-κB signalling pathway. This mechanistic finding provides a pharmacological basis for the use of the A. lancea rhizome in the clinical treatment of various inflammatory conditions.
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http://dx.doi.org/10.1016/j.jep.2021.114183DOI Listing
September 2021

A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes.

Sci Rep 2021 Feb 16;11(1):3850. Epub 2021 Feb 16.

Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China.

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE's anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.
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http://dx.doi.org/10.1038/s41598-021-83435-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886911PMC
February 2021

A two-herb formula inhibits STAT3 signaling and exerts anti-melanoma effects in cell and animal models.

J Ethnopharmacol 2021 Mar 8;268:113671. Epub 2020 Dec 8.

Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China. Electronic address:

Ethnopharmacological Relevance: Malignant melanoma is a fatal cancer. Signal transducer and activator of transcription 3 (STAT3) has been proposed as a therapeutic target of melanoma. An herbal formula Huai-Hua-San (HHS) comprising Sophorae Flos (SF) and Gardeniae Fructus (GF) is traditionally used for treating cancers including melanoma, but the pharmacological basis is unknown.

Aims Of This Study: This study aimed to investigate the anti-melanoma effects of an ethanolic extract of HHS (HHSE), and explore the involvement of STAT3 signaling in the effects.

Materials And Methods: An UPLC-TOF/MS method was developed to control the quality of HHSE. A B16F10 allograft mouse model and three melanoma cell lines (B16F10, A375 and A2058) were used to determine the anti-melanoma effects of HHSE. Dacarbazine (DTIC) and Stattic were used as positive controls. Cell viability was detected using MTT and crystal violet staining assays. Cell apoptosis was analyzed by flow cytometry after the cells were stained with Annexin-V/PI. Cell invasive ability was examined using the transwell assay. Protein levels were determined by Western blotting.

Results: The contents of crocin I, crocin II, quercetin and kaempferol in HHSE were 0.59%, 0.98%, 4.66% and 1.15%, respectively. A clinically relevant dose of HHSE (0.1 g/kg/day, i.g. for 15 consecutive days) significantly suppressed B16F10 tumor growth in mice. HHSE dose-dependently reduced cell viability and dampened invasion of, and induced apoptosis in, melanoma cells. Mechanistic studies revealed that HHSE inhibited the phosphorylation/activation of STAT3 in B16F10 allografts and in cultured melanoma cells. In cell models, HHSE also inhibited the phosphorylation of STAT3 upstream kinases, JAK2 (Tyr1007/1008) and Src (Tyr416), lowered STAT3 nuclear levels, and down-regulated the protein levels of STAT3-targeted molecules. Over-activation of STAT3 in A375 cells significantly attenuated the cytotoxic effects of HHSE.

Conclusions: HHSE exhibits anti-melanoma effects in cell and mouse models. Inhibition of STAT3 signaling contributes to the anti-melanoma mechanisms of HHSE. Our findings lay a groundwork for developing HHSE as a modern agent for melanoma management, and provide pharmacological justifications for the traditional use of HHS in treating melanoma.
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http://dx.doi.org/10.1016/j.jep.2020.113671DOI Listing
March 2021

Assessment of acute pancreatitis severity via determination of serum levels of hsa-miR-126-5p and IL-6.

Exp Ther Med 2021 Jan 9;21(1):26. Epub 2020 Nov 9.

Department of Critical Care Medicine, Jinjiang Hospital of Traditional Chinese Medicine, Jinjiang, Fujian 362200, P.R. China.

Early assessment of acute pancreatitis (AP) severity is key to its treatment. The present study aimed to explore the role of microRNAs (miRNAs/miRs) combined with inflammatory factors in determining AP severity. For this, serum pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-8 and IL-10)] and miRNAs [ (hsa)-miR-548d-5p, hsa-miR-126-5p and hsa-miR-130b-5p] were detected in patients with mild AP (MAP), severe AP (SAP) and recurrent AP (RAP). High expression of IL-10, TNF-α, hsa-miR-126-5p, hsa-miR-548d-5p and hsa-miR-130b-5p was able to distinguish SAP from MAP and RAP (P<0.05). Multifactorial binary logistic regression analysis indicated that IL-1/IL-6 combined with hsa-miR-126-5p/hsa-miR-548d-5p had a significant influence on AP and AP severity (P<0.05). Receiver operating characteristic analysis revealed that IL-1 combined with hsa-miR-126-5p [area under the curve (AUC), 0.926; sensitivity, 90.0%; specificity, 86.7%, P<0.001] and IL-6 combined with hsa-miR-126-5p (AUC, 0.952; sensitivity, 93.3%; specificity, 90.0%; P<0.001) were able to better distinguish MAP from SAP than IL-1/IL-6 combined with hsa-miR-548d-5p, lipase, and amylase. IL-1 or IL-6 combined with hsa-miR-548d-5p (AUC, 0.924; sensitivity, 83.3%; specificity, 93.3%; P<0.001) were able to better distinguish SAP from RAP than IL-1/IL-6 combined with hsa-miR-126-5p, lipase, and amylase. IL-1 combined with hsa-miR-126-5p (AUC, 0.926; sensitivity, 90.0%; specificity, 86.7%; P<0.001) and IL-6 combined with hsa-miR-126-5p (AUC, 0.952; sensitivity, 93.3%; specificity, 90.0%; P<0.001) were able to better differentiate between MAP and RAP than IL-1/IL-6 combined with hsa-miR-548d-5p, lipase, and amylase. These results demonstrated that the combined detection of serum IL-6 and hsa-miR-126-5p may be useful for the early prediction of AP classification.
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http://dx.doi.org/10.3892/etm.2020.9458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690249PMC
January 2021

Prenatal maternal stress and autistic-like behaviours in Chinese preschoolers.

Stress Health 2021 Aug 6;37(3):476-487. Epub 2020 Dec 6.

Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Exposure to prenatal maternal stress (PNMS) has been implicated as a risk factor for a range of psychiatric disorders in children. However, there have been a few studies showing inconsistent associations between PNMS and offspring autistic-like behaviours. We therefore aimed to examine whether trimester-specific PNMS exposure might be related to an increased risk of autistic-like behaviours among preschoolers. Using data from Longhua Children Cohort Study, mothers of 65,931 preschool children were asked to recall their level of PNMS in each of the three trimesters of pregnancy, while children's current autistic-like behaviours were assessed using the Autism Behaviour Checklist. A series of Cox regression models were fitted to assess the association between PNMS exposure and autistic-like behaviours. After adjusting for potential confounders, the Cox regression models showed that PNMS exposure, especially during the second pregnant trimester, was significantly and positively associated with the presence of children's autistic-like behaviours. The strength of these associations was enhanced with the increase of PNMS exposure level. Furthermore, based on different permutations of exposure versus no exposure in each trimester, the participants were divided into eight groups. A cross-over analysis confirmed the aforementioned finding that the second pregnant trimester might be the sensitive period for PNMS exposure increasing the risk of autistic-like behaviours. Our findings supported the hypothesis of an association between PNMS exposure and autistic-like behaviours among preschoolers. Preventive interventions should be trialled to examine whether minimizing maternal psychological stress during pregnancy, especially the second trimester, may reduce the risk of offspring autistic-like behaviours.
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http://dx.doi.org/10.1002/smi.3011DOI Listing
August 2021

Screen time and autistic-like behaviors among preschool children in China.

Psychol Health Med 2021 06 23;26(5):607-620. Epub 2020 Nov 23.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Screen time is becoming increasingly common in daily life. Early and excessive screen use has raised growing concerns for children's neuropsychological development. The purpose of this study was to evaluate the association between exposure to screen time in early life and the presence of autistic-like behaviors among preschool children. 29,461 child-caregiver dyads at kindergartens in Longhua New District of Shenzhen, China, were enrolled in this cross-sectional study. Information concerning socio-demographic characteristics, frequency and duration of children's electronic screen exposure for each year since birth, and autistic-like behaviors (measured by the Autism Behavior Checklist) were collected using a self-administered structured questionnaire completed by the primary caregivers. A series of logistic regression models assessed the association between screen time and autistic-like behaviors. Results indicated that younger initial age, longer daily screen time and longer cumulative years of screen exposure since birth were associated with the presence of autistic-like behaviors at preschool age. The risk was enhanced with the increase of both daily screen time and cumulative years of screen exposure during preschool period. Moreover, the cross-over analysis indicated that the first three years following birth might be a sensitive period for children when screen exposure increases the risk of experiencing autistic-like behaviors. In conclusion, our study implied that screen exposure in early life might increase the occurrence of autistic-like behaviors among preschoolers. These findings support the need for early interventions into preschoolers' screen use, however longitudinal studies are necessary to further confirm the causal relationship between early screen time and the incidence of later autistic-like behaviors among preschool children.
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http://dx.doi.org/10.1080/13548506.2020.1851034DOI Listing
June 2021

Twenty-four-week oral dosing toxicities of Herba Siegesbeckiae in rats.

BMC Complement Med Ther 2020 Nov 11;20(1):341. Epub 2020 Nov 11.

Research and Development Centre for Natural Health Products, HKBU Shenzhen Research and Continuing Education, Shenzhen, China.

Background: Herba Siegesbeckiae (HS), the dried aerial parts of Siegesbeckia orientalis L., S. pubescens Makino, or S. glabrescens Makino, is traditionally used for treating chronic diseases in China. However, there is no information about the chronic toxicity of HS. The objective of this study is to evaluate the 24-week oral dosing toxicities of HS aqueous extract (HSE) in rats.

Methods: S. orientalis-originated HS was reflux-extracted with distilled water. Sprague-Dawley rats were randomly divided into four groups, with 10 males and 10 females in each group. The rats were intragastrically administered with HSE at 5, 1.67 and 0.56 g/kg (experimental groups) or an equal volume of distilled water (control group), 6 days a week, for 24 weeks. The high dose of HSE (5 g/kg) was its maximum tolerated dose. Body weight was recorded every 2 days during the experimental period. Chemical, hematological and histopathological parameters, as well as organ weights, were measured at the end of the experiment.

Results: Decreased body weight gain; increased liver and lung relative weights; histopathological alterations in liver and lung tissues; elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found after HSE treatments. In liver tissues, HSE treatment upregulated levels of three pro-inflammatory cytokines: IL-6, IL-1β and TNF-α. In lung tissues, HSE treatment caused oxidative stress and activated mitogen-activated protein kinases (MAPKs).

Conclusion: Long-term oral administration of HSE caused toxicities in rats evidenced by decreased body weight gain, as well as liver and lung damage. Treatment-induced oxidative stress, inflammation and MAPK activation are involved in HSE's toxicities. Caution should be taken when using HS to treat chronic diseases.
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http://dx.doi.org/10.1186/s12906-020-03137-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661185PMC
November 2020

Early Electronic Screen Exposure and Autistic-Like Behaviors among Preschoolers: The Mediating Role of Caregiver-Child Interaction, Sleep Duration and Outdoor Activities.

Children (Basel) 2020 Oct 28;7(11). Epub 2020 Oct 28.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

Research into early screen exposure has raised growing concerns about its impact upon children's neuropsychological well-being. However, possible pathways remain unclear. This study therefore aimed not only to evaluate the association between screen exposure during the ages of 0-3 years and preschoolers' autistic-like behaviors, but also the mediating roles of the frequency of caregiver-child interaction, sleep duration and level of participation in outdoor activities. Based on the 2017 survey of the Longhua Child Cohort Study, data of 29,595 child-caregiver dyads were obtained via a caregiver-reported questionnaire, with the data from 29,461 dyads included in the data analysis. Multiple linear and logistic regression models were employed to estimate the associations between screen exposure, caregiver-child interaction, sleep duration, outdoor activities, and children's autistic-like behaviors. The results indicated that screen exposure during 0-3 years of age was associated with the presence of autistic-like behaviors at preschool age, and the strength of the association was enhanced with the increase of average daily screen time (Odds Ratios (ORs) ranging from 1.358 to 4.026). The frequency of caregiver-child interaction and sleep duration mediated 5.32% and 1.19% of the variance of the association respectively, but outdoor activities did not mediate the association. Our findings indicate that preschoolers who are exposed to screens at aged 0-3 years might have an increased risk of autistic-like behaviors, and that, the frequency of caregiver-child interaction and sleep duration might function as potential mediators of this association.
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http://dx.doi.org/10.3390/children7110200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692375PMC
October 2020

Corrigendum to "A two-herb formula inhibits osteoclastogenesis and suppresses NF-kB and MAPK pathways" [Journal of Ethnopharmacology 252 (2020) 112,625].

J Ethnopharmacol 2021 Jan 9;265:113312. Epub 2020 Sep 9.

Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China; Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/j.jep.2020.113312DOI Listing
January 2021

Gomisin N Exerts Anti-liver Cancer Effects and Regulates PI3K-Akt and mTOR-ULK1 Pathways in Vitro.

Biol Pharm Bull 2020 ;43(8):1267-1271

Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University.

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.
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http://dx.doi.org/10.1248/bpb.b20-00030DOI Listing
May 2021

Modulation of the Astrocyte-Neuron Lactate Shuttle System contributes to Neuroprotective action of Fibroblast Growth Factor 21.

Theranostics 2020 9;10(18):8430-8445. Epub 2020 Jul 9.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, PR China.

A viewpoint considering Alzheimer's disease (AD) as "type 3 diabetes" emphasizes the pivotal role of dysfunctional brain energy metabolism in AD. The hormone fibroblast growth factor 21 (FGF21) is a crucial regulator in energy metabolism; however, our understanding of the therapeutic potential and mechanisms underlying the effect of FGF21 on neurodegeneration of AD is far from complete. To further elucidate the effect of FGF21 on AD-related neurodegeneration, we used APP/PS1 transgenic mice to assess the effects of FGF21 on memory dysfunction, amyloid plaque pathology and pathological tau hyperphosphorylation. We also established an system to mimic astrocyte-neuron communication and an model of acute injury. Based on the and models, we analyzed the neuroprotective actions of FGF21 and pathways related to astrocyte-neuron communication and further focused on the astrocyte-neuron lactate shuttle system. Here, we report that FGF21 can ameliorate Alzheimer-like neurodegeneration in APP/PS1 transgenic mice. We detected defects in the astrocyte-neuron lactate shuttle system in the and models of AD and identified FGF21 as a neuroprotective molecule that can rescue these deficits. Administration of FGF21 can alleviate memory dysfunction, amyloid plaque pathology and pathological tau hyperphosphorylation, and the function of FGF21 in neurodegeneration is mediated in part by monocarboxylate transporters (MCTs). evidence also suggests that FGF21 acts centrally in mice to exert its effects on neurodegeneration and energy metabolism its regulation of MCTs. These results suggest that FGF21 alters metabolic parameters to mediate its neuroprotective functions. Modulation of the astrocyte-neuron lactate shuttle system can be one of the most efficient strategies for FGF21 in Alzheimer-like degeneration and contributes to improvements in brain metabolic defects and amyloid β-induced cytotoxicity. Our findings provide insights into the mechanisms underlying the effects of FGF21 on neurodegeneration and brain energy metabolism and suggest that FGF21 may have therapeutic value in the treatment of AD and other neurodegenerative diseases.
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http://dx.doi.org/10.7150/thno.44370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381735PMC
May 2021

An herbal formula inhibits STAT3 signaling and attenuates bone erosion in collagen-induced arthritis rats.

Phytomedicine 2020 May 30;76:153254. Epub 2020 May 30.

Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China; Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; JaneClare Transdermal TCM Therapy Laboratory, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address:

Background: Receptor activator of NF-κB ligand (RANKL) facilitates differentiation of osteoclast precursors into osteoclasts, resulting in bone erosion in rheumatoid arthritis (RA) patients. Fibroblast-like synoviocytes (FLS) are the main cells for producing RANKL. Signal transducer and activator of transcription 3 (STAT3) signaling is activated in FLS of RA patients (RA-FLS), which has been linked to RANKL production. A two-herb formula (RL) comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos is traditionally used for treating RA in China. We have found that a standardized ethanolic extract of RL (RLE for short) alleviates bone erosion in collagen-induced arthritis (CIA) rats.

Purpose: This study aimed to determine whether RLE inhibits RANKL production and osteoclastogenesis in cell and rat models, and to explore the involvement of the STAT3 pathway in this inhibition.

Study Design And Methods: A CIA rat model, interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS and a co-culture system (IL-6/sIL-6R-stimulated RA-FLS/peripheral blood mononuclear cells) were used to evaluate the effects of RLE. Micro-computed tomography analysis was used to observe bone erosion in CIA rats. Tartrate-resistant acid phosphatase staining was used to evaluate osteoclastogenesis. Western blotting and ELISA assays were employed to examine protein levels. RT-qPCR was used to detect mRNA levels. STAT3-over-activated RA-FLS were used to investigate the involvement of STAT3 signaling in the anti-osteoclastogenic effects of RLE.

Results: RLE alleviated bone erosion in joints of CIA rats. In both synovial tissues of CIA rats and IL-6/sIL-6R-stimulated RA-FLS, RLE downregulated the protein level of RANKL. In the co-culture system, RLE significantly and dose-dependently inhibited IL-6/sIL-6R-induced osteoclastogenesis. Mechanistic studies revealed that RLE lowered the protein level of phospho-STAT3 (Tyr705) in synovial tissues of CIA rats. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited the activation/phosphorylation of a STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008) and STAT3 (Tyr705), decreased the nuclear localization of STAT3, lowered mRNA levels of STAT3-transcriptionally regulated genes IL-1β and TNF-α. RLE's inhibitory effects on RANKL production in RA-FLS gradually decreased when IL-6/sIL-6R doses increased. Over-activation of STAT3 diminished the inhibitory effects of RLE on RANKL production in IL-6/sIL-6R-stimulated RA-FLS, and attenuated the anti-osteoclastogenic effects of RLE in the co-culture system.

Conclusion: We, for the first time, demonstrated that suppressing STAT3 signaling contributes to the inhibition of RANKL production and osteoclastogenesis, and thereby supports the mechanisms responsible for the reduction in bone erosion in RLE-treated CIA rats. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug, and supports the notion that targeting STAT3 signaling is a viable strategy for managing bone erosion.
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http://dx.doi.org/10.1016/j.phymed.2020.153254DOI Listing
May 2020

A traditional Chinese medicine formula inhibits tumor growth in mice and regulates the miR-34b/c-Met/β-catenin pathway.

J Ethnopharmacol 2020 Oct 4;260:113065. Epub 2020 Jun 4.

Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China; Jane Clare Transdermal TCM Therapy Laboratory, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address:

Ethnopharmacology Relevance: Si-Jun-Zi-Tang (SJZT) is a traditional Chinese medicine formula used to treat chronic and debilitating diseases including melanoma. SJZT-based therapies have achieved good clinical outcomes in melanoma management. However, the pharmacological basis of SJZT for its clinical use in melanoma treatment is not fully understood.

Aim Of The Study: To investigate the anti-melanoma effects and mechanism of action of an ethanolic extract of SJZT.

Materials And Methods: SJZT was extracted using 50% ethanol. A murine B16 melanoma-bearing mouse model was employed to investigate the anti-melanoma effects of SJZT. microRNA (miRNA) and mRNA levels were examined by RT-qPCR, and protein levels were measured by Western blotting.

Results: SJZT significantly inhibited B16 tumor growth in mice. Mechanistic investigations revealed that SJZT elevated miR-34b (a tumor suppressing miRNA), and lowered c-Met (a miR-34b target gene) and β-catenin (a downstream molecule of c-Met signaling) expression levels in the B16 tumors.

Conclusions: In this study we found, for the first time, that SJZT exerts anti-melanoma effects and regulates the miR-34b/c-Met/β-catenin pathway in a melanoma mouse model. Our findings provide pharmacological justifications for the clinical use of SJZT in treating melanoma.
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http://dx.doi.org/10.1016/j.jep.2020.113065DOI Listing
October 2020

Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression.

Cell Death Dis 2020 04 20;11(4):246. Epub 2020 Apr 20.

Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.

Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial-mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.
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http://dx.doi.org/10.1038/s41419-020-2440-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171093PMC
April 2020

Inhibiting the Src/STAT3 signaling pathway contributes to the anti-melanoma mechanisms of dioscin.

Oncol Lett 2020 Mar 17;19(3):2508-2514. Epub 2020 Jan 17.

School of Chinese Medicine, Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Kowloon 999077, Hong Kong, SAR, P.R. China.

Late stage melanoma is associated with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3) is currently a target for melanoma treatment as it is constitutively activated with high frequency in melanoma. Dioscin is a natural steroid saponin that is present in several medical herbs. A previous study demonstrated that dioscin inhibits STAT3 signaling in a cerebral ischemia-reperfusion injury rat model. Furthermore, dioscin has been reported to exert anti-melanoma effects in B16 melanoma cells and a B16 allograft mouse model. The present study investigated whether inhibition of STAT3 signaling is involved in the anti-melanoma effects of dioscin. The results of the present study demonstrated that dioscin significantly decreased viability, induced apoptosis and suppressed migration of human A375 melanoma cells and murine B16F10 melanoma cells. Furthermore, dioscin inhibited the phosphorylation of STAT3 and Src (an upstream kinase of STAT3), and downregulated mRNA levels of STAT3-targeted genes, including B-cell lymphoma-2, cyclin D1 and matrix metalloproteinase-2. In addition, overexpression of STAT3 decreased the anti-proliferative effects of dioscin. Overall, the results of the present study indicate that inhibiting the Src/STAT3 signaling pathway contributes to the anti-melanoma molecular mechanisms of dioscin. These results provide further pharmacological groundwork for developing dioscin as a novel anti-melanoma agent.
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http://dx.doi.org/10.3892/ol.2020.11315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039043PMC
March 2020

Therapeutic Effects of Lithospermate B Complexed with Mg or Zn on Metabolic Syndrome Induced in Rats Fed with High-Fat Diet.

Molecules 2020 Feb 22;25(4). Epub 2020 Feb 22.

Graduate Institute of Biotechnology, National Chung-Hsing University, Taichung 402, Taiwan.

Excessive food consumption and insufficient exercise lead to the prevalence of metabolic syndrome in modern life, which consequently increases the risk of many chronic diseases. Magnesium lithospermate B (MLB) from Danshen has been demonstrated to improve metabolic changes in high-fat diet-fed rats with metabolic syndrome. In this study, Mg in MLB was successfully replaced with Zn to form zinc lithospermate B (ZLB) complex. MLB (10 mg/kg /day) and ZLB of various concentrations (1, 2.5, 5, and 10 mg/kg/day) were prepared and examined for their therapeutic effects on metabolic syndrome induced in rats fed with a high-fat diet. The results showed that both MLB and ZLB were able to recover or alleviate the abnormal physiological states of high-fat diet-fed rats including weight gain, epididymal fat accumulation, fatty liver, retarded blood lipid and glucose metabolism putatively caused by insulin resistance, and elevated levels of proinflammatory cytokine, leptin, and oxidative stress. In an overall view of the animal study, the effectiveness of ZLB supplementation seemed to be better than that of MLB supplementation for the recovery of high-fat-fed rats from metabolic syndrome.
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http://dx.doi.org/10.3390/molecules25040983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070705PMC
February 2020

Chrysoeriol ameliorates TPA-induced acute skin inflammation in mice and inhibits NF-κB and STAT3 pathways.

Phytomedicine 2020 Mar 19;68:153173. Epub 2020 Jan 19.

Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong; Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China; JaneClare Transdermal TCM Therapy Laboratory, Hong Kong Baptist University, Kowloon Tong, Hong Kong. Electronic address:

Background: Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells.

Purpose: This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects.

Study Design And Methods: A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues.

Results: In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1β and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model.

Conclusion: We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.
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http://dx.doi.org/10.1016/j.phymed.2020.153173DOI Listing
March 2020

A two-herb formula inhibits osteoclastogenesis and suppresses NF-kB and MAPK pathways.

J Ethnopharmacol 2020 Apr 25;252:112625. Epub 2020 Jan 25.

Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China; Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/j.jep.2020.112625DOI Listing
April 2020

Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways.

Toxins (Basel) 2019 11 26;11(12). Epub 2019 Nov 26.

Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

Alpha-momorcharin (α-MMC), a member of the ribosome-inactivating protein (RIP) family, has been found in the seeds of (bitter melon). α-MMC contributes a number of pharmacological activities; however, its inflammatory properties have not been well studied. Here, we aim to determine the inflammatory responses induced by recombinant α-MMC and identify the underlying mechanisms using cell culture and animal models. Recombinant α-MMC was generated in Rosetta™(DE3)pLysS and purified by the way of nitrilotriacetic acid (NTA) chromatography. Treatment of recombinant α-MMC at 40 μg/mL exerted sub-lethal cytotoxic effect on THP-1 monocytic cells. Transcriptional profiling revealed that various genes coding for cytokines and other proinflammatory proteins were upregulated upon recombinant α-MMC treatment in THP-1 cells, including MCP-1, IL-8, IL-1β, and TNF-α. Recombinant α-MMC was shown to activate IKK/NF-κB and JNK pathways and the α-MMC-induced inflammatory gene expression could be blocked by IKKβ and JNK inhibitors. Furthermore, murine inflammatory models further demonstrated that α-MMC induced inflammatory responses in vivo. We conclude that α-MMC stimulates inflammatory responses in human monocytes by activating of IKK/NF-κB and JNK pathways, raising the possibility that consumption of α-MMC-containing food may lead to inflammatory-related diseases.
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http://dx.doi.org/10.3390/toxins11120694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949964PMC
November 2019

Gold nano-mesh synthesis by continuous-flow X-ray irradiation.

J Synchrotron Radiat 2019 Nov 23;26(Pt 6):1929-1935. Epub 2019 Sep 23.

Department of Engineering Science, National Cheng Kung University, Tainan 70101, Taiwan.

X-ray irradiation has been extensively used in recent years as a fabrication step for nanoparticles and nanoparticle systems. A variant of this technique, continuous-flow X-ray irradiation, has recently been developed, and offers three important advantages: precise control of the irradiation dose, elimination of convection effects in the precursor solution, and suitability for large-scale production. Here, the use of this method to fabricate Au nano-meshes of interest as transparent and flexible electrodes for optoelectronics is reported. The study includes extensive characterization of the synthesis parameters and of the product properties, with rather encouraging results.
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http://dx.doi.org/10.1107/S1600577519011834DOI Listing
November 2019

MiR-let-7a/f-CCR7 signaling is involved in the anti-metastatic effects of an herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos in melanoma.

Phytomedicine 2019 Nov 5;64:153084. Epub 2019 Sep 5.

Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong; Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China; JaneClare Transdermal TCM Therapy Laboratory, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address:

Background: Metastasized melanoma is extremely difficult to treat. Activation of C-C chemokine receptor type 7 (CCR7) has been linked to melanoma metastasis. CCR7 can be directly regulated by miR-let-7. We have previously shown that an ethanolic extract of an herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos (SLE) inhibits melanoma cell migration and invasion.

Purpose: In this study, we determined whether SLE suppresses melanoma metastasis, and whether regulation of miR-let-7a/f-CCR7 signaling is involved in the effect.

Study Design And Methods: Small RNA sequencing was conducted to compare miRNA expression profiles of B16F10 tumors dissected from SLE-treated or untreated mice. Western blot and RT-qPCR analyses were employed to examine protein and miRNA levels, respectively. A B16F10 melanoma lung metastasis mouse model was used to evaluate the effects of SLE on melanoma metastasis. MiR-let-7a/f-knockdown and CCR7-overexpression cell models were used to investigate the involvement of miR-let-7a/f-CCR7 signaling in the anti-metastatic effects of SLE.

Results: It was found that SLE upregulated levels of miR-let-7a/f in B16F10 melanoma tissues. SLE significantly elevated levels of miR-let-7a/f, lowered the protein level of CCR7, inhibited the phosphorylation of CCR7 downstream molecules p38 and JNK in B16F10 and A375 melanoma cells. SLE inhibited B16F10 melanoma lung metastasis in mice. SLE upregulated levels of miR-let-7a/f, and lowered protein levels of CCR7, MMP-2, MMP-9, phospho-p38 (Thr180/Tyr182) and phospho-JNK (Thr183/Tyr185) in melanoma-invaded lung tissues. Knockdown of miR-let-7a/f diminished the effects of SLE on CCR7 signaling in, and invasion of, melanoma cells. Overexpression of CCR7 lessened the effects of SLE in inhibiting the phosphorylation of p38 and JNK in, and the invasive capability of, melanoma cells.

Conclusion: We for the first time demonstrated that SLE inhibits melanoma metastasis in mice, and that regulation of the miR-let-7a/f-CCR7 pathway contributes to the anti-metastatic mechanisms of SLE. These findings provide a pharmacological basis for developing SLE as a modern agent for treating metastatic melanoma. Additionally and importantly, this study suggests that regulating the miR-let-7a/f-CCR7 pathway is a novel strategy for controlling melanoma metastasis.
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http://dx.doi.org/10.1016/j.phymed.2019.153084DOI Listing
November 2019

A TCM formula comprising Sophorae Flos and Lonicerae Japonicae Flos alters compositions of immune cells and molecules of the STAT3 pathway in melanoma microenvironment.

Pharmacol Res 2019 04 20;142:115-126. Epub 2019 Feb 20.

Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, Hong Kong, China; JaneClare Transdermal TCM Therapy Laboratory, Hong Kong Baptist University, Hong Kong, China. Electronic address:

A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been linked to the development of melanoma immunosuppressive microenvironment. In this work, we investigated whether SLE inhibits melanoma growth by reprogramming the tumor microenvironment in mouse and co-culture cell models. In B16F10 melanoma-bearing mice, we found that intragastric administration of SLE (1.2 g/kg) dramatically inhibited tumor growth. This observation was associated with the downregulation of protein levels of phospho-STAT3 (Tyr 705) and STAT3-regulated immunosuppressive cytokines, and mRNA levels of STAT3-targeted genes involved in tumor growth and immune evasion. We also observed increased Th, Tc and dendritic cells in the melanomas and spleens in SLE-treated mice compared to that in control mice. In a co-culture system composed of B16F10 cells and mouse primary splenic lymphocytes, it was found that SLE not only inhibited STAT3 activation in B16F10 cells, but also downregulated mRNA levels of STAT3-targeted genes in the splenic lymphocytes. In this co-culture setting, SLE decreased the levels of STAT3-regulated immunosuppressive cytokines, increased the percentages of Th, Tc and dendritic cells as well. Furthermore, effects of SLE on STAT3 phosphorylation, cytokine levels and immune cell subtype percentages were significantly weaker in the B16 cells (stable cells harboring a constitutively active STAT3 variant STAT3C)/splenic lymphocytes co-culture system than in the B16 cells (cells stably transfected with the empty vector)/splenic lymphocytes co-culture system, indicating that STAT3 over-activation diminishes SLE's effects. In summary, our findings indicate that reprograming the immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. This study provides further pharmacological groundwork for developing SLE as a modern agent for melanoma prevention/treatment, and supports the notion that reprograming immunosuppressive microenvironment is a viable anti-melanoma strategy.
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http://dx.doi.org/10.1016/j.phrs.2019.02.020DOI Listing
April 2019

Clinical application of immunomagnetic reduction for quantitative analysis of beta-subunit of human chorionic gonadotropin in blastocyst culture media to differentiate embryo quality.

Clin Chim Acta 2019 Apr 16;491:46-51. Epub 2019 Jan 16.

Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.

Background: The most important factor for a successful pregnancy after in vitro fertilization is embryo quality. The aim of this study was to explore the possibility that using the immunomagnetic reduction (IMR) assay to quantitatively measure β-subunit of human chorionic gonadotropin (β-hCG) in blastocyst culture media to differentiate embryo quality.

Methods: This was a prospective case-control study including 28 samples of blastocyst culture media. We used single-step blastocyst culture and IMR assay to analyze β-hCG concentrations in culture media. We also explored the relationship between IMR signals of β-hCG and morphological grading of blastocysts.

Results: β-hCG concentration-dependent IMR signals were highly correlated with blastocyst morphological quality (Spearman correlation coefficient: 0.731). Receiver-operating characteristic curve analysis showed a cut-off IMR value to differentiate embryo quality of 0.873%, with an area under the curve of 0.947, sensitivity of 0.882 and specificity of 0.818. Furthermore, subanalysis also revealed a positive correlation between β-hCG concentration-dependent IMR signals and trophectoderm grading, with a Spearman correlation coefficient of 0.576.

Conclusions: An IMR assay can quantitatively measure β-hCG in blastocyst culture media, and may be a potential clinical tool to assist in the assessment of good blastocyst quality before embryo transfer.
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http://dx.doi.org/10.1016/j.cca.2019.01.012DOI Listing
April 2019

Mycelia Exert Anti-liver Cancer Effects and Inhibit STAT3 Signaling and .

Front Pharmacol 2018 17;9:1449. Epub 2018 Dec 17.

Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Hepatocellular carcinoma (HCC), the major form of primary liver cancer, is a common cause of cancer-related death worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in HCC and has been proposed as a chemotherapeutic target for HCC. (AC), a medicinal mushroom unique to Taiwan, is traditionally used for treating HCC. Whereas natural AC is scarce, cultured AC mycelia are becoming alternatives. In this study, we investigated the anti-HCC effects of the ethyl acetate fraction of an ethanolic extract of AC mycelia (EEAC), particularly exploring the involvement of STAT3 signaling in these effects. We found that EEAC reduced cell viability, induced apoptosis, and retarded migration and invasion in cultured HepG2 and SMMC-7721 cells. Immunoblotting results showed that EEAC downregulated protein levels of phosphorylated and total STAT3 and JAK2 (an upstream kinase of STAT3) in HCC cells. Real-time PCR analyses showed that STAT3, but not JAK2, mRNA levels were decreased by EEAC. EEAC also lowered the protein level of nuclear STAT3, decreased the transcriptional activity of STAT3, and downregulated protein levels of STAT3-targeted molecules, including anti-apoptotic proteins Bcl-xL and Bcl-2, and invasion-related proteins MMP-2 and MMP-9. Over-activation of STAT3 in HCC cells diminished the cytotoxic effects of EEAC. In SMMC-7721 cell-bearing mice, EEAC (100 mg/kg, i.g. for 18 days) significantly inhibited tumor growth. Consistent with our data, EEAC induced apoptosis and suppressed JAK2/STAT3 activation/phosphorylation in the tumors. Taken together, EEAC exerts anti-HCC effects both and ; and inhibition of STAT3 signaling is, at least in part, responsible for these effects. We did not observe significant toxicity of EEAC in normal human liver-derived cells, nude mice and rats. Our results provide a pharmacological basis for developing EEAC as a safe and effective agent for HCC management.
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http://dx.doi.org/10.3389/fphar.2018.01449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304454PMC
December 2018

Substituting one Paris for another? In vitro cytotoxic and in vivo antitumor activities of Paris forrestii, a substitute of Paris polyphylla var. yunnanensis.

J Ethnopharmacol 2018 May 15;218:45-50. Epub 2018 Feb 15.

Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: Chong-lou (Paris polyphylla var. yunnanensis or P. polyphylla var. chinensis) is traditionally used as an anticancer medicine in China. It is also the material basis of some Chinese patent anticancer medicines, such as Gan-Fu-Le capsules, Bo-Er-Ning capsules, Lou-Lian capsules, Ruan-Jian oral liquid, and Qi-Zhen capsules. P. forrestii, a substitute for Chong-lou, is planted at a large scale in the Yunnan Province of China.

Aim Of The Study: To clarify the active chemical constituents of P. forrestii and evaluate the in vitro and in vivo anticancer activities of the total saponins from P. forrestii.

Materials And Methods: The total saponins of P. forrestii were extracted and separated to yield pure compounds by chromatographic techniques, and the structures of the isolates were elucidated by spectroscopic methods. The cytotoxicity of the crude extracts, total saponins, and chemical constituents were evaluated using an MTS assay. In vivo antitumor activities of the total saponins from P. forrestii were measured using H22 tumor-bearing mice by intraperitoneal (ip) administration.

Results: Eight compounds, including polyphyllin D (1), formosanin C (2), dioscin (3), diosgenin-3-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranoside (4), paris saponin H (5), pennogenin-3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→4)]-β-d-glucopyranoside (6), pariposide A (7), and crustecdysone (8), were isolated from the total saponins of P. forrestii. The total saponins and compounds 1-6 showed significant inhibitory activity against the growth of the HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines. The total saponins from P. forrestii had a tumor-inhibitory effect in H22 tumor-bearing mice upon ip (2.25 mg/kg dose) administration, with an inhibition rate of 42.6% compared with cisplatin (ip, 2 mg/kg dose, 53.9% inhibition rate).

Conclusion: The results support that P. forrestii could be a substitute for P. polyphylla var. yunnanensis as an anticancer medicine.
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http://dx.doi.org/10.1016/j.jep.2018.02.022DOI Listing
May 2018

Sex Difference of Angiotensin IV-, LVV-Hemorphin 7-, and Oxytocin-Induced Antiallodynia at the Spinal Level in Mice With Neuropathic Pain.

Anesth Analg 2018 06;126(6):2093-2101

Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.

Background: We demonstrated previously that angiotensin IV (Ang IV) and LVV-hemorphin 7 (LVV-H7) act through the blockade of insulin-regulated aminopeptidase to decrease oxytocin degradation, thereby causing antihyperalgesia at the spinal level in rats. We determined that intrathecal oxytocin can induce significant antihyperalgesia in male rats with inflammation but not in female rats. Thus, we speculate that Ang IV, LVV-H7, and oxytocin can induce antiallodynia, which could be of great therapeutic potential. Because the antihyperalgesia by using these peptides was with sex difference, their possible antiallodynia was examined in male and female mice for comparison. We investigated whether Ang IV, LVV-H7, and oxytocin produce antiallodynia at the spinal level in mice and whether this antiallodynia differs between the sexes.

Methods: Partial sciatic nerve ligation surgery was performed on adult male and female C57BL/6 mice from the same litter (25-30 g). The effects of intrathecal injections of Ang IV (25.8 nmol), LVV-H7 (27.2 nmol), and oxytocin (0.125 or 1.25 nmol) were assessed through the von Frey test 3 days after partial sciatic nerve ligation.

Results: Intrathecal injection of Ang IV, LVV-H7, and oxytocin all produced a potent antiallodynia in male mice. However, these antiallodynia effects were either extremely weak or absent in female mice at the same dose.

Conclusions: Intrathecal Ang IV, LVV-H7, and oxytocin can all cause significant antiallodynia in male mice. The Ang IV-, LVV-H7-, and oxytocin-induced antiallodynia effects differed between the sexes at the spinal level in mice.
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http://dx.doi.org/10.1213/ANE.0000000000002795DOI Listing
June 2018

Effect of teapot materials on the chemical composition of oolong tea infusions.

J Sci Food Agric 2018 Jan 10;98(2):751-757. Epub 2017 Aug 10.

Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.

Background: The flavor and quality of tea are widely believed to be associated with the pot in which the tea is made. However, this claim is mostly by experiences and lacks solid support from scientific evidence. The current study investigated and compared the chemical compositions of oolong tea made with six different teapot materials, namely Zisha, Zhuni, stainless steel, ceramic, glass and plastic.

Results: For each tea sample, polyphenols and caffeine were examined by HPLC-UV, volatile compounds by GC/MS, amino acids by LC/MS and minerals by ICP-MS. The results suggested that tea infusions from Zisha and Zhuni pots contain higher levels of EGC, EGCG and total catechins and less caffeine than those from ceramic, glass and plastic pots and tend to have the lowest total mineral contents, potassium and volatile compounds in tea soup. The statistical differences were not all significant among Zisha, Zhuni and stainless steel pots.

Conclusion: Based on the overall chemical composition of the tea infusion, Yixing clay pots (Zisha and Zhuni) produce tea infusions that are presumably less bitter and more fragrant and tend to contain more healthful compounds than tea infusions from other pots. The results could partially explain why Yixing clay pots are among the most popular teapots. The beneficial effects of long-term repeated use of these teapots warrants further study. © 2017 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.8522DOI Listing
January 2018

An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling .

Front Pharmacol 2017 28;8:227. Epub 2017 Apr 28.

Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, China.

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effects of AR. Results showed that AR reduced cell viability, induced cell apoptosis, and suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells. Mechanistic studies showed that AR potently suppressed STAT3 and Src phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells. AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP-2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect of AR was diminished by overexpressing STAT3C, a persistent active variant of STAT3. In conclusion, AR exerted anti-CRC effects and these effects are at least in part attributed to the inhibition of STAT3 signaling. Our findings provide a molecular justification for the traditional use of AR in treating CRC, and a pharmacological basis for developing AR-derived modern anti-CRC agent(s).
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http://dx.doi.org/10.3389/fphar.2017.00227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408070PMC
April 2017
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