[Research progress in mechanism of puerarin in treating vascular dementia].

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aß injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Hyperspectral imaging with machine learning for non-destructive classification of Astragalus membranaceus var. mongholicus, Astragalus membranaceus, and similar seeds.

The roots of Astragalus membranaceus var. mongholicus (AMM) and A. membranaceus (AM) are widely used in traditional Chinese medicine. Although AMM has higher yields and accounts for a larger market share, its cultivation is fraught with challenges, including mixed germplasm resources and widespread adulteration of commercial seeds. Current methods for distinguishing Astragalus seeds from similar (SM) seeds are time-consuming, laborious, and destructive. To establish a non-destructive method, AMM, AM, and SM seeds were collected from various production areas. Machine vision and hyperspectral imaging (HSI) were used to collect morphological data and spectral data of each seed batch, which was used to establish discriminant models through various algorithms. Several preprocessing methods based on hyperspectral data were compared, including multiplicative scatter correction (MSC), standard normal variable (SNV), and first derivative (FD). Then selection methods for identifying informative features in the above data were compared, including successive projections algorithm (SPA), uninformative variable elimination (UVE), and competitive adaptive reweighted sampling (CARS). The results showed that support vector machine (SVM) modeling of machine vision data could distinguish Astragalus seeds from SM with >99% accuracy, but could not satisfactorily distinguish AMM seeds from AM. The FD-UVE-SVM model based on hyperspectral data reached 100.0% accuracy in the validation set. Another 90 seeds were tested, and the recognition accuracy was 100.0%, supporting the stability of the model. In summary, HSI data can be applied to discriminate among the seeds of AMM, AM, and SM non-destructively and with high accuracy, which can drive standardization in the Astragalus production industry.

Effect of Whey Protein Supplementation in Postmenopausal Women: A Systematic Review and Meta-Analysis.

(1) Background: Whey protein (WP) in combination with resistance training (RT) is beneficial in improving sarcopenic obesity and its damaging effects in older adults, while the difference between men and women should be considered while interpreting results. This review aims to investigate WP's efficacy on postmenopausal women with or without RT; (2) Material and Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library from inception to August 2021 for randomized controlled trials that included comparison groups to evaluate WP's efficacy in women aged 55 years and above. The outcomes included body composition, muscular strength, functional capacity, and dietary intake. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to estimate the effect of WP. We also performed subgroup analysis with or without RT; (3) Results: We included 14 studies in the systematic review and 10 studies in the meta-analysis. Subgroup analyses showed RT was a major confounder for muscle strength, lean mass, and dietary protein intake (PI). In the RT subgroup, WP supplementation had a significant positive effect on biceps curl strength (BC) (SMD: 0.6805, 95% CI: 0.176, 1.185, I2: 0%), and lower limb lean-mass (LLLM) (SMD: 1.103, 95% CI: 0.632, 1.574, I2: 14%). In the subgroup without RT, a significant negative effect on PI (SMD: -0.4225, 95% CI: -0.774, -0.071, I2: 47%) was observed, while no significant effect on muscle strength or lean mass was revealed. WP supplementation did not show a significantly different effect on fat mass or body weight loss in both the subgroups; (4) Conclusions: In postmenopausal women, WP supplementation only in combination with RT enhances BC and LLLM compared to placebo controls. Without RT, WP has no significant benefit on muscle strength or lean mass.

Effects of the Chinese herbal medicine Hong Huang decoction, on myocardial injury in breast cancer patients who underwent anthracycline-based chemotherapy.

Objective: To assess the effects of Hong Huang Decoction (HHD), a Chinese herbal medicine, on myocardial injury in breast cancer patients who underwent anthracycline (ANT)-based chemotherapy. Methods: A total of 51 patients with breast cancer who underwent an ANT-based chemotherapy program and met the inclusion/exclusion criteria were allocated to the treatment or placebo groups using a random number generation process. Patients in the treatment group received liquid HHD twice a day. Treatment was given from 1 day prior to chemotherapy up to the end of chemotherapy (after 6 months). Participants in the placebo group received a placebo over the same schedule. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diagnostic markers of acute myocardial infarction [e.g., lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and B-type natriuretic peptide (BNP)], nitric oxide (NO), superoxide dismutase (SOD), as well as pro-inflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and human C-reactive protein (CRP)], and anti-inflammatory cytokine interleukin-10 (IL-10), were outcome measures assessed before chemotherapy, 3 and 6 months after chemotherapy. Results: Compared to the placebo group, the GLS value was significantly higher in the treatment group (19.95 ± 1.16 vs. 19.06 ± 1.64, P ≤ 0.001). Significant differences were also noted for levels of SOD (689.71 ± 203.60 vs. 807.88 ± 182.10, P < 0.05), IL-6 (58.04 ± 22.06 vs. 194.20 ± 40.14, P ≤ 0.001), IL-10 (237.90 ± 94.98 vs. 68.81 ± 32.92, P ≤ 0.001), NO (75.05 ± 26.39 vs. 55.83 ± 19.37, P ≤ 0.005), and TNF-α (301.80 ± 134.20 vs. 680.30 ± 199.60, P ≤ 0.001) in the patients before chemotherapy compared to 6 months after initiating chemotherapy. Conclusion: HHD regulated the levels of IL-6, IL-10, SOD, NO, and TNF-α. The results demonstrated that GLS is a better indicator of early myocardial injury compared to LVEF, and HHD could modulate oxidative stress to protect against ANT cardio toxicity. Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR1900022394. Date of registration: 2019-04-09.

Revealing the metabolic mechanism of dandelion extract against A549 cells using UPLC-QTOF MS.

Dandelion extract exhibits potential anticancer activity and is expected to be a new type of natural anticancer drug. However, the effect mechanism of dandelion extract to lung cancer cells is still unclear. Here, untargeted metabolomics approach based on LC-MS was used to characterize the metabolic responses of A549 cells to dandelion extract exposure and to provide new clues for the antitumor mechanism of dandelion extract from the metabolomics perspective. A total of 16 differentially expressed and time-related metabolites were identified between dandelion extract exposure and control groups. The perturbed metabolic pathways of A549 cells after dandelion extract exposure mainly include the glycerophospholipid metabolism and purine metabolism. These results concluded that dandelion extract may exert anticancer activity by affecting malignant proliferation, disturbing the stability of cell membrane structure, reducing the adhesion of tumor cells to extracellular matrix and fibronectin, and finally inducing tumor cell death.

Targets and underlying mechanisms related to the sedative and hypnotic activities of saponins from Rhodiola rosea L. (crassulaceae).

Rhodiola rosea L. (Crassulaceae) are popularly used as a natural supplement for the treatment of insomnia and anxiety. Here, saponin extracts from R. rosea were investigated for their roles on relieving sleeplessness. The levels of neurotransmitters, hormones, and inflammation cytokines in plasma, and the expression of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), prostaglandin D2 (PGD2), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the hypothalamus and hippocampus were detected using ELISA, RT-PCR, and western blotting. First, the butanol fraction extracted from R. rosea was collected as the total saponins (HJT-I), then a saponin-rich fraction (HJT-II) was obtained after the further purification of HJT-I. The saponin contents of HJT-I and HJT-II were 28.92% and 65.69%, respectively. Second, behavioral tests were performed and showed that both HJT-I and HJT-II could effectively reduce the duration of immobility in the tail suspension test, and shorten sleep latency and prolong the sleep duration time in the sodium barbital-induced sleeping test, with HJT-II better than HJT-I. Third, ELLISA results showed that the concentrations of GABA, 5-HT, norepinephrine (NA), PGD2, and IL-1ß in plasma were significantly increased after HJT-I and HJT-II administration, while IL-6 was decreased. HJT-I and HJT-II also exhibited differential modulation of the receptors of 5-HT, GABA, PGD2, and IL-1ß expression. In hypothalamus, HJT-II was more powerful than HJT-I in regulation of the GABAARα2, GABAARα3, and glutamic acid decarboxylase (GAD) 65/67 expression, as well as 5-HT2A and IL-1ß. As for DPR and PGD2, HJT-II was more effective in the hippocampus. The efficacy of HJT-I was better than HJT-II at stimulating GABAARα2, GAD 65/67, 5-HT1A, and IL-1ß expression in the hippocampus. In conclusion, the potential sedative and hypnotic effects of HJT-I and HJT-II may possibly be related to the serotonergic, GABAAergic, and immune systems, while the underlying mechanism of HJT-I and HJT-II differed from each other.

Inhibitory effect of chloroform extracts from Citrus aurantium L. var. amara Engl. on fat accumulation.

BACKGROUND: Excess lipid accumulation can accelerate the development of various metabolic diseases. Blossoms of Citrus aurantium L. var. amara Engl. (CAVA) have been reported to possess inhibitory capacities on lipid deposition. However, the constituents responsible for the observed bioactivity and the underlying mechanisms are still not clearly understood. PURPOSE: To screen constituents from blossoms of CAVA with inhibitory effects on lipid accumulation and to explore the action mechanism. METHODS: The chloroform (CHL) extracts are prepared from blossoms of CAVA by fractional extraction and are characterized using LC-MS assay. 3T3-L1 preadipocytes are induced with differentiation medium (DMI) and treated with CHL extracts. High fat diet (HFD)-induced obese mice are further established and administrated with CHL extracts for 12 weeks. Hematoxylin and eosin (HE) staining, Oil Red O staining, ELISA, RT-qPCR, western blot and 16S rRNA gene sequence methods are employed. RESULTS: 14 compounds are identified in CHL extracts and trigonelline hydrochloride, nobiletin and 7-demethylsuberosin are most abundant. CHL extracts treatment significantly inhibit differentiation of 3T3-L1 cells by regulating expression of preadipocyte factor-1 (Pref-1), fatty acid synthase (FAS) and CCAAT/enhancer binding protein α (C/EBPα). CHL extracts intervention also significantly attenuate features of obesity and improved plasma biochemical profiles in HFD-fed mice. HFD-triggered hepatic steatosis and epididymal adipose tissues (EATs) hypertrophy are also reversed by CHL extracts administration through enhancing antioxidant responses and modulating lipogenesis and energy expenditure-related genes and proteins. 16S rRNA gene sequence data further show that CHL extracts enhance the diversity of gut microbiota. CHL extracts at lower concentrations reduce the ratio of Firmicutes to Bacteroidetes and the abundance of Erysipelotrichaceae. CHL extracts at higher doses markedly increase the abundance of Lachnospiraceae. CONCLUSION: These findings suggest that CHL extracts probably suppress lipid accumulation through inhibiting differentiation of 3T3-L1 cells and attenuating metabolic syndromes in HFD-fed mice.

[Traditional use of Paris polyphylla and its active components].

This paper reviewed the traditional use of Paris polyphylla and its active components, aiming to provide reference for the development and utilization of this plant. It was found that P. polyphylla has been used as a medicinal plant by eight ethnic minorities. A total of 62 experiential effective recipes, including 29 simple recipes and 33 compound recipes, were analyzed for their indications, traditional processing methods, medicinal compatibilities, and administration doses. The top three in the eight ethnic minorities sorted by the quantity of folk recipes were the Yi nationality(18), Naxi nationality(13) and Bai nationality(12). P. polyphylla has been widely employed for the treatment of nine categories of diseases, especially the dermatologic diseases, trauma, and toxicosis currently. The collating of material basis for its traditional functions revealed 26 active components, among which 19 were steroidal saponins capable of resisting cancer, furuncles, carbuncles, abscesses, bacteria, inflammation and stopping bleeding. This study preliminarily proved the efficacy of P. polyphylla in treating cancer and respiratory system, digestive system, and genitourinary system diseases, which has provided clues for related basic research of P. polyphylla and development of new preparations.

Traditional use of Paris polyphylla and its active components / 中国中药杂志

This paper reviewed the traditional use of Paris polyphylla and its active components, aiming to provide reference for the development and utilization of this plant. It was found that P. polyphylla has been used as a medicinal plant by eight ethnic minorities. A total of 62 experiential effective recipes, including 29 simple recipes and 33 compound recipes, were analyzed for their indications, traditional processing methods, medicinal compatibilities, and administration doses. The top three in the eight ethnic minorities sorted by the quantity of folk recipes were the Yi nationality(18), Naxi nationality(13) and Bai nationality(12). P. polyphylla has been widely employed for the treatment of nine categories of diseases, especially the dermatologic diseases, trauma, and toxicosis currently. The collating of material basis for its traditional functions revealed 26 active components, among which 19 were steroidal saponins capable of resisting cancer, furuncles, carbuncles, abscesses, bacteria, inflammation and stopping bleeding. This study preliminarily proved the efficacy of P. polyphylla in treating cancer and respiratory system, digestive system, and genitourinary system diseases, which has provided clues for related basic research of P. polyphylla and development of new preparations.

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats.

Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs-RAGE interaction.

Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient-Derived Xenografts.

There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer. Metformin (150 mg/kg) as a single agent inhibits the growth of both PDX tumors by at least 50% (P < 0.05) when administered orally for 24 days. In one of the PDX models, metformin given concurrently with 5-FU (25 mg/kg) leads to an 85% (P = 0.054) growth inhibition. Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. In addition, we also performed genetic characterizations of serial PDX samples with corresponding parental tissues from patients using next-generation sequencing (NGS). Our pilot NGS study demonstrates that PDX represents a useful platform for analysis in cancer research because it demonstrates high fidelity with parental tumor. Furthermore, NGS analysis of PDX may be useful to determine genetic identifiers of drug response. This is the first preclinical study using PDX and PDX-derived organoids to investigate the efficacy of metformin in colorectal cancer. Mol Cancer Ther; 16(9); 2035-44. ©2017 AACR.

[Study about Traditional Chinese Medicine syndrome of adolescent neck pain].

OBJECTIVE: To preliminarily research the formular about the Traditional Chinese Medicine (TCM) syndrome of adolescent neck pain. METHODS: An observation table of adolescent neck pain syndromes was formulated,and 1 397 patients with adolescent neck pain were investigated to establish a database of adolescent neck pain. The Descriptive Statistical Analysis and Hierarchical Cluster Analysis were performed by statistical software. RESULTS: Totally 60 TCM symptoms was clustered into 4 TCM syndromes by Hierarchical Cluster Analysis. The expert panel of TCM syndromes preliminarily formulate 4 TCM syndromes of adolescent neck pain by analyzing the result of Cluster Analysis and discussing their clinical experience. CONCLUSION: Adolescent neck pain is a category of Tendon Trauma's Bi-syndrome of TCM. Ying, Wei, Qi and blood block caused by exopathy, strains, and internal injury is considered as the main pathogenesis of adolescent neck pain. Base on statistical result and expert's opinions, 4 TCM syndromes about adolescent neck pain were formulated: cold-dampness syndrome, dampness-heat blockage syndrome, liver-stagnation and spleen-deficiency syndrome, Qi and Yin deficiency of both heart and kidney syndrome.

Origin and evolution of China Pharmacopoeia and its implication for traditional medicines.

Traditional Chinese Medicine (TCM) has a history that can be dated back to several thousand years ago. The extant earliest medical book is Huangdi Neijing (Canon of Internal Medicine, 770 BC~221 BC), and the earliest pharmacy monograph is Shengnong Bencao Jing (Shengnong Materia Medica, AD25~AD220). The most influential pharmacy monograph is the Bencao Gangmu (Compendium of Materia Medica, AD1368~AD1644). There were also many other far-reaching influencial monographs, which become the main and the most important derived resources of modern China pharmacopoeia for TCM. In this paper, we try to introduce some representative medicine and pharmacy works of ancient China, and elaborate the origin, development and improvement process of modern China pharmacopoeia, which may have referential significance for traditional and natural drugs. China Pharmacopoeia and TCM still have to face many problems in authenticity discrimination, action mechanism, and adverse reaction, etc. The improvement of China Pharmacopoeia still has room for progress with the solutions of modern analytical methods to the problems. The start-up and development of Herbalomics project will be helpful to further improve the China Pharmacopoeia, especially Chinese patented medicine and compound prescription.

Study about Traditional Chinese Medicine syndrome of adolescent neck pain / 中国骨伤

<p><b>OBJECTIVE</b>To preliminarily research the formular about the Traditional Chinese Medicine (TCM) syndrome of adolescent neck pain.</p><p><b>METHODS</b>An observation table of adolescent neck pain syndromes was formulated,and 1 397 patients with adolescent neck pain were investigated to establish a database of adolescent neck pain. The Descriptive Statistical Analysis and Hierarchical Cluster Analysis were performed by statistical software.</p><p><b>RESULTS</b>Totally 60 TCM symptoms was clustered into 4 TCM syndromes by Hierarchical Cluster Analysis. The expert panel of TCM syndromes preliminarily formulate 4 TCM syndromes of adolescent neck pain by analyzing the result of Cluster Analysis and discussing their clinical experience.</p><p><b>CONCLUSION</b>Adolescent neck pain is a category of Tendon Trauma's Bi-syndrome of TCM. Ying, Wei, Qi and blood block caused by exopathy, strains, and internal injury is considered as the main pathogenesis of adolescent neck pain. Base on statistical result and expert's opinions, 4 TCM syndromes about adolescent neck pain were formulated: cold-dampness syndrome, dampness-heat blockage syndrome, liver-stagnation and spleen-deficiency syndrome, Qi and Yin deficiency of both heart and kidney syndrome.</p>

A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine.

Berberine (BBR), a traditional Chinese herbal medicine, was shown to display anticancer activity. In this study, we attempted to provide a global view of the molecular pathways associated with its anticancer effect through a gene expression-based chemical approach. BBR-induced differentially expressed genes obtained from the Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) were analyzed using the Connectivity Map (CMAP) database to compare similarities of gene expression profiles between BBR and CMAP compounds. Candidate compounds were further analyzed using the Search Tool for Interactions of Chemicals (STITCH) database to explore chemical-protein interactions. Results showed that BBR may inhibit protein synthesis, histone deacetylase (HDAC), or AKT/mammalian target of rapamycin (mTOR) pathways. Further analyses demonstrated that BBR inhibited global protein synthesis and basal AKT activity, and induced endoplasmic reticulum (ER) stress and autophagy, which was associated with activation of AMP-activated protein kinase (AMPK). However, BBR did not alter mTOR or HDAC activities. Interestingly, BBR induced the acetylation of α-tubulin, a substrate of HDAC6. In addition, the combination of BBR and SAHA, a pan-HDAC inhibitor, synergistically inhibited cell proliferation and induced cell cycle arrest. Our results provide novel insights into the mechanisms of action of BBR in cancer therapy.

Protective effects of diphenylheptanes from Curcuma phaeocaulis Val. on H2O2 induced cell injury.

Curcuma phaeocaulis Val. has been used as a health food in China for a long time. This research aimed to isolate and identify its active compounds with protective effects against hydrogen peroxide-induced PC12 cell death. 70% ethanol extracts of C. phaeocaulis were re-extracted and three fractions of water, petroleum ether and ethyl acetate were obtained. Three diphenylheptane compounds from the ethyl acetate fraction were identified for the first time from C. phaeocaulis, and compound III was considered to be a new structure. All of the three compounds displayed certain protective effects against toxicity in PC12 cells. For all concentrations, compound III displayed a more significant protective effect than ethanol extracts, the ethyl acetate fraction, and the other two compounds. At a concentration of 50 µg mL(-1), the survival rate of damaged PC-12 cells treated with compound III reached 84.7%. Diphenylheptanes were concluded to be the main compounds responsible for the health effects of C. phaeocaulis.

Expression of a gene encoding ß-ureidopropionase is critical for pollen germination in tomatoes.

Global warming has seriously decreased world crop yield. High temperatures affect development, growth and, particularly, reproductive tissues in plants. A gene encoding ß-ureidopropionase (SlUPB1, EC 3.5.1.6) was isolated from the stamens of a heat-tolerant tomato (CL5915) using suppression subtractive hybridization. SlUPB1 catalyzes the production of ß-alanine, the only ß-form amino acid in nature. In the anthesis stage, SlUPB1 expression in CL5915 stamens, growing at 35/30°C (day/night), was 2.16 and 2.93 times greater than that in a heat-sensitive tomato (L4783) cultivated at 30/25°C or 25/20°C, respectively. Transgenic tomatoes, upregulating SlUPB1 in L4783 and downregulating SlUPB1 in CL5915, were constructed, and the amount of ß-alanine measured by liquid chromatography-electrospray ionization-mass spectrometry in the transgenic overexpression of SlUPB1 was higher than that of L4783. However, the ß-alanine in the transgenics downregulating SlUPB1 was significantly lower than the ß-alanine of CL5915. Pollen germination rates of these transgenics were analyzed under different developmental and germinating temperatures. The results indicated that germination rates of transgenics overexpressing SlUPB1 were higher than germination rates of the background tomato L4783. Germination rates of transgenics downregulating SlUPB1 were significantly lower than germination rates of background tomato CL5915, indicating the necessity of functional SlUPB1 for pollen germination. Pollen germinating in the buffer with the addition of ß-alanine further indicated that ß-alanine effectively enhanced pollen germination in tomatoes with low SlUPB1 expression. Together, these results showed that the expression of SlUPB1 is important for pollen germination, and ß-alanine may play a role in pollen germination under both optimal and high temperatures.

Synthesis and anti-HBV activity of novel 3'-N-phenylsulfonyl docetaxel analogs.

Nine new 3'-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg secretion than the positive control lamivudine. Further extensive SAR and mechanistic studies will be reported in due course.