Holistic quality evaluation of Callicarpae Formosanae Folium by multi-chromatography-based qualitative and quantitative analysis of polysaccharides and small molecules.

Callicarpae Formosanae Folium (CFF), derived from the leaves of Callicarpa formosana Rolfe, is a common Chinese medicinal herb used for the treatment of hematemesis. Phytochemical studies found that phenylpropanoids, flavonoids, terpenoids and polysaccharides were the main ingredients of CFF. However, there is limited scientific information concerning holistic quality method and quality consistency evaluation of CFF. In this study, a strategy integrating HPGPC-ELSD, HPLC-PDA, UV-VIS and UPLC-QTOF-MS/MS was firstly developed to simultaneously qualify and quantify polysaccharides, as well as representative small molecules in CFF. HPGPC-ELSD was applied to characterize the molecular weight distribution of polysaccharides, HPLC-PDA was developed to qualitatively and quantitatively determine monosaccharides. UV-VIS was used to determine the total polysaccharides content, and UPLC-QTOF-MS/MS was established to characterize the small molecules. The quality consistency of commercial CFF (CM-CFF) was also evaluated. It was shown that the relative molecular weights, the compositional monosaccharides and small molecules composition in CM-CFF and self-collected CFF (SC-CFF) samples were similar. A total of 32 small molecules including 6 phenylpropanoids, 7 flavonoids and 19 terpenoids were characterized in CFF. However, the variation was observed in the content of polysaccharides, luteolin, ursolic acid, as well as total contents of terponoids in CM-CFF samples, which implied that the holistic quality of CM-CFF was inconsistent. The results suggested that the proposed evaluation strategy could be applied as a potential approach for the quality control of CFF. And the quality of CM-CFF should be improved by Good Agriculture Practice (GAP) base and standard processing method.

Er-Xian decoction attenuates ovariectomy-induced osteoporosis by modulating fatty acid metabolism and IGF1/PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Er-Xian decoction (EXD) is a traditional Chinese medicine (TCM) formula used to treat osteoporosis (OP). However, the anti-OP mechanism of EXD has not yet been fully elucidated. AIM OF THE STUDY: The study aimed to verify the anti-OP effect of EXD and to explore its underlying mechanism. METHODS: The anti-OP targets and mechanisms of EXD were predicted by network pharmacological analysis. Then, an ovariectomized (OVX) rat model was established to validate the key anti-OP mechanism of EXD. Firstly, the therapeutic effect of EXD on OP was confirmed using micro-CT bone analysis, pathological observation, and ELISA detection. Secondly, serum metabolites related to key biological processes were detected using an automatic biochemical analyzer and GC-MS. Finally, ELISA, qRT-PCR, and western blot were utilized to further explore the potential key anti-OP pathway of EXD. RESULTS: A total of 159 anti-OP targets of EXD were identified. Functional annotation revealed that OP treatment using EXD was associated with lipid metabolism, fatty acid (FA) metabolism, and PI3K/AKT signaling pathway. Experimental studies confirmed that EXD ameliorated ovariectomy-induced bone loss and bone microstructure deterioration. EXD treatment also upregulated the level of serum estrogen and downregulated the level of OC, PⅠNP, CTX-1, TC, and LDL-C. Besides, principal component analysis (PCA) and heat map of serum FAs distinguished OVX rats from the SHAM and EXD groups. Serum concentrations of important n-3 FAs, including C20:3N3, C20:5N3, and C22:5N3, were significantly increased in the EXD group. The increased stearoyl-CoA desaturase 1 (SCD1) index 1 and index 2 in the OVX group were reversed by EXD administration. Additionally, EXD reversed the decreased serum IGF1 level and tibia IGF1R, PI3K, and AKT expression in OVX rats. CONCLUSION: EXD ameliorated ovariectomy-induced bone loss by modulating lipid metabolism, FA metabolism, and IGF1/PI3K/AKT pathway.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Monascin abrogates RANKL-mediated osteoclastogenesis in RAW264.7 cells via regulating MAPKs signaling pathways.

Osteoclasts (OCs) are multinucleated cells that play a major role in osteolytic diseases such as osteoporosis. Monascin (Ms) is one of the active substances in the traditional Chinese medicine red yeast rice. Studies have found that red yeast rice can maintain bone health. In this study, the anti-osteoclastogenesis effects of Ms on RANKL-induced RAW264.7 cells were assessed, and the underlying mechanism was investigated. Ms exhibited inhibitory effects on OC differentiation and formation in a dose-dependent manner and suppressed the bone-resorbing activity of mature OCs. Ms blocked OCs-typical genes (c-Fos, NFATc1, CSTK, MMP-9, TRAP, ITG-ß3, OSCAR and DC-STAMP). Furthermore, Ms treatment considerably inhibited the activation of MAPKs, JNK and p38. Taken together, Ms suppresses RANKL-induced osteoclastogenesis of RAW264.7 cells by restraining MAPKs signaling pathways and is a potential therapeutic option as a novel OC inhibitor to mitigate bone erosion.

Exploring the Potential Mechanism of Artemisinin and Its Derivatives in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking.

Objective: This study is aimed at predicting and contrasting the mechanisms of artemisinin (ARS), dihydroartemisinin (DHA), artesunate (ART), artemether (ARM), and arteether (ARE) in the treatment of osteoporosis (OP) using network pharmacology and molecular docking. Methods: The targets of ARS, DHA, ART, ARM, and ARE were obtained from the SwissTargetPrediction. The targets related to OP were obtained from the TTD, DrugBank, Genecards, and DisGeNet databases. Then, the anti-OP targets of ARS, DHA, ART, ARM, and ARE were obtained and compared using the Venn diagram. Afterward, the protein-protein interaction (PPI) networks were built using the STRING database, and Cytoscape was used to select hub targets. Moreover, molecular docking validated the binding association between five molecules and hub targets. Finally, GO enrichment and KEGG pathway enrichment were conducted using the DAVID database. The common pathways of five molecules were analysed. Results: A total of 28, 37, 36, 27, and 33 anti-OP targets of ARS, DHA, ART, ARM, and ARE were acquired. EGFR, EGFR, CASP3, MAPK8, and CASP3 act as the top 1 anti-OP targets of ARS, DHA, ART, ARM, and ARE, respectively. MAPK14 is the common target of five molecules. All five molecules can bind well with these hubs and common targets. Meanwhile, functional annotation showed that MAPK, Serotonergic synapse, AMPK, prolactin, and prolactin signaling pathways are the top 1 anti-OP pathway of ARS, DHA, ART, ARM, and ARE, respectively. IL-17 signaling pathway and prolactin signaling pathway are common anti-OP pathways of five molecules. Besides, GO enrichment showed five biological processes and three molecular functions are common anti-OP mechanisms of five molecules. Conclusion: ARS, DHA, ART, ARM and ARE can treat OP through multi-targets and multi pathways, respectively. All five molecules can treat OP by targeting MAPK14 and acting on the IL-17 and prolactin signaling pathways.

Factors affecting the follow-up time after a positive result in the fecal occult blood test.

In 2010, Taiwan included the fecal occult blood test (FOBT) under preventive health insurance services. For patients whose test positive, receiving follow-ups is paramount. This study investigated factors affecting the follow-up time of these patients. This retrospective study used data from the colorectal cancer screening archives. The study period was from 2010 to 2013, and the subjects were 50-75-year-old persons who tested positive for FOBT. The t test, one-way ANOVA, and multiple regression were performed to address the differences in the mean tracking period between variables such as the population's demographic characteristics. The mean follow-up time for the 98,482 participants whose screening results were positive exhibited significant differences (p < 0.001) according to medical unit region and classification, age, screening location, family history, examination method, and diagnosis. The model predicting the mean follow-up time predicted a period of 10.079 days longer for those whose hospital was on an offshore island than that of those whose hospital was in the eastern regions. The follow-up time was 1.257 days shorter for people who were inpatients than those who were outpatients and was 8.902 days longer for people who underwent double contrast barium enema plus flexible sigmoidoscopy than those who underwent other examination methods. Patients with a family history of colorectal cancer and those whose examination results indicated cancer had a follow-up time of 2.562 and 2.476 days shorter than those who did not know their family history and those with other results, respectively. Factors affecting the follow-up time of people whose FOBT results were positive consisted of the location and classification of the follow-up institution, age, screening location, family history, examination method, and diagnosis. This provides valuable references for improving the cancer screening program.

Effect of Coptis chinensis on Biofilm Formation and Antibiotic Susceptibility in Mycobacterium abscessus.

Mycobacterium abscessus infections are notoriously difficult to be treated and newer treatment options are required. Coptis chinensis (C. chinensis) and its main compound berberine are frequently used to treat bacterial and viral infections. In this study, the susceptibility of M. abscessus to C. chinensis extract and berberine was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) evaluation. The effects of C. chinensis and berberine on biofilm formation and antibiotic susceptibility in M. abscessus were observed. C. chinensis at concentrations of MIC (1.5 mg/mL) and 2 × MIC (3.0 mg/mL) and berberine at ½ × MIC (0.125 mg/mL) demonstrated a strong inhibition of biofilm formation. Concentration of C. chinensis at ½ × MIC resulted in a significant reduction in MICs of trimethoprim/sulfamethoxazole (TMP/SXT), clarithromycin (CLA), and linezolid (LZD). Similarly, ½ × MIC berberine had a significant effect on the MIC reductions of nine antibiotics including TMP/SXT, CLA, and LZD. Notably, the resistance level MIC of LZD against M. abscessus was reversed to a susceptible level by treatment with either C. chinensis or berberine. Therefore, C. chinensis and berberine have the potential to produce a synergistic antimycobacterial effect, reduce biofilm formation, and decrease antibacterial resistance to LZD in M. abscessus.

Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve.

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC50 values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 µg/mL, 16 µg/mL, and 500 µg/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice.

OBJECTIVE: To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice. METHODS: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction. RESULTS: Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05). CONCLUSIONS: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice.@*METHODS@#Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction.@*RESULTS@#Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05).@*CONCLUSIONS@#ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

Combinational strategy for high-performance cancer chemotherapy.

The clinical outcomes of conventional mono-chemotherapy of cancers are usually far from satisfactory due to some issues such as tumor heterogeneity and resistance to chemotherapeutic drugs. With the increasing knowledge of molecular signal pathways and pathological mechanisms involved in the initiation and progression of cancers, collaborative strategies have been elaborated to optimize therapeutic outcomes. This review surveys the most recent advances in combination therapy including combination chemotherapy, chemotherapy plus gene therapy, chemotherapy plus phototherapy, as well as chemotherapy plus immunotherapy. Additionally, chemotherapy-involved multiple therapy that merges various therapeutic modalities is also presented. We try to elicit the rationales of applying these combinational formulations for cancer chemotherapy, which might provide new guidelines for high-performance cancer treatments.

Proteomics analysis reveals a potential new target protein for the lipid-lowering effect of Berberine8998.

Berberine8998 is a newly synthesized berberine derivative with better lipid-lowering activity and improved absorption. The objective of this study was to investigate the effects of berberine8998 on serum cholesterol and lipid levels in vivo and to examine the mechanisms involved. Hamsters on high-fat diet (HFD) were administered berberine or berberine8998 (50 mg·kg-1·d-1, ig) for 3 weeks. Berberine8998 administration significantly lowered the total cholesterol, triglycerides and LDL-C levels in HFD hamsters. Bioinformatics revealed that berberine and berberine8998 shared similar metabolic pathways and fatty acid metabolism was the predominant pathway. Western blot validation results showed that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and long-chain fatty acid-CoA ligase 1 (ACSL1), two proteins involved in fatty acid metabolism, were expressed differently in the berberine8998 group than in the untreated group and the berberine treatment group. Biochemistry results showed that berberine8998 significantly lowered the non-esterified fatty acid (NEFA) levels, which may lead to a reduction in TG levels in the berberine8998 treatment group and the differences observed in proteomics analyses. Pharmacokinetic analysis conducted in rats. After administration of berberine or berberine8998 (50 mg/kg, ig), berberine8998 exhibited a remarkably improved absorption with increasing bioavailability by 6.7 times compared with berberine. These findings suggest that berberine8998 lowers cholesterol and lipid levels via different mechanisms than berberine, and its improved absorption makes it a promising therapeutic candidate for the treatment of hypercholesterolemia and obesity.

Tetrahydroxystilbene Glucoside (TSG) Restores the Effect of Transient Hypoxia on Reperfusion Injury in Senescent H9c2 Cells by Regulating Mitochondrial Energy Metabolism.

Tetrahydroxystilbene glucoside (TSG) is extracted from a famous Chinese herbal medicine which is widely used as an antiaging agent in history. Lots of studies gave evidence that TSG exhibited benefits to brain, like improvement of learning and memory and synaptic plasticity. Moreover, the polyphenolic structure of TSG enables its capability to prevent cerebral ischemia/reperfusion injury (IRI) by reducing apoptosis and ROS/RNS generation. Due to its antioxidant profile, TSG had been demonstrated to alleviate cardiac toxicity by regulating biochemical indexes and ROS. However, whether TSG exhibited cardioprotective effects via mitochondrial energy metabolic functions, which played crucial role in IRI, remained unclear. Here, we used an in vitro aging model of cardiomyocytes to evaluate the effects of TSG on transient hypoxia-pretreated hypoxia/reoxygenation (H/R) injury and mitochondrial energy metaolism. Our results showed that TSG enhanced cardioprotective effect of transient hypoxia on H/R by reducing excessive ROS production and calcium overloading. Significant improvements of mitochondrial respiratory functions and ketone body metabolism elucidated that TSG restored the effect of transient hypoxia on H/R injury in aging cardiomyocytes via upregulating mitochondrial energy metabolism.

Immunomodulatory Effects of Taiwanese Neolitsea Species on Th1 and Th2 Functionality.

Neolitsea species, medicinal plants belonging to Lauraceae, contain rich alkaloids, steroids, sesquiterpenoids, and triterpenoids which possess antimicrobial, antioxidant, and anti-inflammatory bioactivities. However, species differences in the immunomodulatory effects and evidence pertaining to the effects of Neolitsea species on adaptive immunity are scarce. This study aimed to evaluate the immunomodulatory properties of ten Taiwanese Neolitsea plants on T helper (Th) cell functionality, especially Th1 and Th2. Most of the 29 crude extracts of Neolitsea were not toxic to splenocytes, except N. buisanensis roots. N. aciculata and N. villosa leaf extracts possessed differential immunomodulatory effects on Th1/Th2 balance. N. aciculata var. variabillima and N. hiiranensis leaf extracts attenuated both Th1 and Th2 cytokines while N. konishii dramatically suppressed IFN-γ production. As N. aciculata var. variabillima and N. konishii leaf extracts significantly attenuated Th1 functionality, we further evaluated their effects on CD4 cells under CD3/CD28 stimulation. N. aciculata var. variabillima significantly suppressed IFN-γ, IL-10, and IL-17, demonstrating the broad suppressive effects on T helper cells; N. konishii significantly suppressed IFN-γ and IL-10 production, while the production of IL-17 was not altered. Collectively, these data demonstrated that leaf extracts of Taiwanese Neolitsea species contain phytochemicals with potentials to be developed as selective immunomodulators.

Highly Stretchable and Conductive Copper Nanowire Based Fibers with Hierarchical Structure for Wearable Heaters.

Wearable heaters have been increasingly attracting researchers' great interest due to their efficient utility in maintaining warmth and in thermotherapy. Nowadays carbon nanomaterials and metallic nanowires tend to become the mainstream heating elements in wearable heaters considering their excellent electrical and mechanical properties. Though considerable progress has been made, there still exist challenging issues that need to be addressed in practical applications, including bad breathability and poor endurance to mechanical deformations. Here, we devise a copper nanowire based composite fiber with a unique hierarchical structure. This fiber possesses not only excellent heating performance, but also fantastic tolerance to mechanical impact, such as bending, twisting, and stretching. We further weave these fibers into a wearable heating fabric and realize smart personal heating management through an Android phone by integrating with a microcontroller unit. Two practical applications are demonstrated including a heating kneepad for articular thermotherapy and a heating coat on an infant model for maintaining warmth.

Effect of a complex lutein formula in an animal model for light-induced retinal degeneration.

Several retinal degenerative diseases cause vision loss and retinal cell death. Currently, people face prolonged exposure to digital screens, rendering vision protection from light exposure a critical topic. In this study, we designed a complex lutein formula (CLF) by combining several natural compounds: Calendula officinalis, Lycium barbarum, Vaccinium myrtillus, Cassia obtusifolia, and Rhodiola rosea. In addition, we evaluated the protective effects of the formula on retinal functions in an animal model for light-induced retinal degeneration. We employed electroretinography to analyse retinal function, and conducted a histological examination of the morphological changes in the retina treated under various conditions. We revealed that the retinal function in animals exposed to light for 7 days decreased significantly; however, the retinal function of animals that had received the CLF exhibited superior performance, despite light exposure. In addition, a greater portion of the outer nuclear layer (ONL) (i.e. the nuclei of photoreceptors) in these animals was preserved compared with the animals that had not received the formula after 7 days of light exposure. These results revealed that our dietary CLF supplement attenuated retinal function loss resulting from long-term light exposure.

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids.

BACKGROUND: T cells play a pivotal role in the adaptive immunity that participates in a wide range of immune responses through a complicated cytokine network. Imbalance of T-cell responses is involved in several immune disorders. Neolitsea species, one of the biggest genera in the family Lauraceae, have been employed widely as folk medicines for a long time in Asia. Previous phytochemical investigations revealed the abundance of terpenes in the leaves of N. hiiranensis, an endemic Neolitsea in Taiwan, and demonstrated anti-inflammatory activities. However, the effect of N. hiiranensis on the functionality of immune cells, especially T cells, is still unclear. In this study, we utilize in vitro and in vivo approaches to characterize the effects of leaves of N. hiiranensis and its terpenoids on adaptive immune responses. METHODS: Dried leaves of N. hiiranensis were extracted three times with cold methanol to prepare crude extracts and to isolate its secondary metabolites. The ovalbumin (OVA)-sensitized BALB/c mice were administrated with N. hiiranensis extracts (5-20 mg/kg). The serum and splenocytes of treated mice were collected to evaluate the immunomodulatory effects of N. hiiranensis on the production of OVA-specific antibodies and cytokines. To further identify the N. hiiranensis-derived compounds with immunomodulatory potentials, OVA-primed splenocytes were treated with compounds isolated from N. hiiranensis by determining the cell viability, cytokine productions, and mRNA expression in the presence of OVA in vitro. RESULTS: Crude extracts of leaves of N. hiiranensis significantly inhibited IL-12, IFN-γ, and IL-2 cytokine productions as well as the serum levels of antigen-specific IgM and IgG2ain vivo. Two of fourteen selected terpenoids and one diterpenoid derived from the leaves of N. hiiranensis suppressed IFN-γ in vitro. In addition, ß-caryophyllene oxide attenuated the expression of IFN-γ, T-bet, and IL-12Rß2 in a dose-dependent manner. N. hiiranensis-derived ß-caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN-γ production, and Th1-assocaited genes. CONCLUSION: As IFN-γ is the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that the N. hiiranensis and its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.

[Probing into Second Pathological Factors of Sjögren's Syndrome].

Sjögren's syndrome is a chronic autoimmune disease with unclear etiology. From the point of etiology, Chinese medicine (CM) theory holds that pathological products like dry toxin, blood stasis are produced in the pathological process. They are both pathologic results and pathogenic factors for its further development. So pathological products are also named as second pathogenic factors. In this article, the concept of second pathogenic factors was sorted and defined. Main second pathogenic factors of Sjögren's syndrome were pinpointed, and their modern medical bases were analyzed. Authors came to a conclusion that clearing away second pathogenic factors is a key point in treating Sjögren's syndrome.

[Effect of epigallocatechin gallate against exercise-induced fatigue in mice].

OBJECTIVE: To investigate the effects of epigallocatechin gallate (EGCG)against exercise-induced fatigue in mice. METHODS: Total 120 mice were randomly divided into three groups and tested separately. For each test, there were 30 mice subdivided into high dose (50 mg/kg . d EGCG) and low dose (10 mg/kg . d EGCG) groups as well as saline control group(1 ml/kg . d) with 10 in each. Burden swimming, running wheel endurance, stick climbing and hypoxia tolerance exercise were used to establish fatigue mice training model in three groups. And intraperitoneal injection with different doses of EGCG per day for consecutively 28 days and the mice in the control group were treated with normal saline. After the last each test, the blood lactic acid (BLA), blood urea nitrogen (BUN), blood lactate dehydrogenase (LDH), muscle glycogen (MG) and liver glycogen (LG) of each group of mice were determined. RESULTS: EGCG treatment groups(B and C)revealed a prolonged the mice survival time of burden swimming test, hypoxia tolerance, running wheel time and the ability of stick climbing(P < 0.05 or P <0.01), and increased LDH activity and MG and LG contents, reduced contents of BLA and BUN. High dose group had an obviously increase effect than lower dose group(P <0.05). CONCLUSION: EGCG has significant effects against exercise-induced fatigue in mice.

[HPLC Fingerprints of Nerviliae fordii and Nervilia plicata].

OBJECTIVE: To establish the HPLC fingerprint of the whole plant of Nerviliae fordii and Nervilia plicata, in order to provide a method for evaluation of authenticity and quality control of the whole plant of Nerviliae fordii. METHODS: 15 batches of Nerviliae fordii and 5 batches of Nervilia plicata were analyzed on a Kromasil C18 column (250 mm x 4.6 mm, 5 µm) at room temperature with gradient elution using acetonitrile and 0.2% phosphoric acid as the mobile phase at a flow rate of 1.0 mL/min. The wavelength of detector was 256 nm. RESULTS: Significant differences were found between Nerviliae fordii and Nervilia plicata. Furthermore, there were no obvious differences observed between Nerviliae fordii of big-leaf and Nerviliae fordii of small-leaf. CONCLUSION: The present-developed HPLC fingerprints method provides a rapid, effective and valuable benchmark for distinguishing of Nerviliae fordii and Nervilia plicata, which is favorable to improve overall quality control of Nerviliae Fordii.