Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Integrated Network Pharmacology and In-silico Approaches to Decipher the Pharmacological Mechanism of Dioscorea septemloba Thunb in Treating Gout and Its Complications.

BACKGROUND: Dioscorea septemloba Thunb. (DST) has demonstrated therapeutic potential in the treatment of gout and its associated complications. However, the underlying mechanisms of DST's pharmacological activity remain unclear. This study aims to investigate the pharmacological substances and network regulatory mechanisms of DST in treating gout and its complications using network pharmacology. METHODS: According to ultra-high performance liquid chromatography coupled with hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) data and Lipinski's rule of five, 24 bioactive phytochemicals from DST were identified. The targets of gout were retrieved from Gene Expression Omnibus (GEO), GeneCards, and DisGeNET databases, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) enrichment analysis. The Cytoscape network analysis was used to identify the primary pathological pathways and key targets. Finally, LeDock was used for molecular docking to verify the active components of DST and their core target proteins. RESULTS: DST contains several core active ingredients, such as tetrahydroimidazo[1,2-a]pyridine- 2,5-dione, diosgenin, beta-sitosterol, dioscorol B, montroumarin and 9,10-dihydro-5,7- dimethoxy-3,4-phenanthrenediol. Moreover, these active components were found to strongly bind to the key targets for treating gout and its complications, including HSP90AA1, STAT3, PTGS2, PPARG, MTOR, HIF1A, MMP9, ESR1, and TLR4. As a result, DST alleviates gout and its complications by inhibiting xanthine dehydrogenase (XDH) to reduce uric acid levels and regulating the HIF-1α, EZH2/STAT3, and COX-2/PPAR-γ pathways to reduce inflammation. Additionally, it also plays an analgesic role by regulating the neuroactive ligand-receptor interaction pathway and calcium ion signaling pathway. CONCLUSION: This study has provided insights into the underlying mechanisms of DST in the treatment of gout and its complications, which could serve as a scientific foundation for its clinical translation.

Ratiometric fluorescent probe based on non-conjugated polymer dots for pH measurements in ordinary Portland cement-based materials.

An organic fluorescent probe, citric acid-1,3-Propanediamine-Rhodamine B (CPR) was synthesized to determine pH of ordinary Portland cement requiring only a small sample size (less than 500 µL cement leachate). The SEM, XRD, and FTIR investigations demonstrate that citric acid-1,3-Propanediamine are polymer dots with a fusiform structure. Ratio pH probe is constructed by rhodamine B with polymer dots, which exhibits a linear response in high alkaline range. A 6-fold increase in fluorescence intensity (455 nm) is achieved at pH from 12.00 to 13.25. Combined with measurements of the isothermal calorimeter, mineral composition, and microscopic morphology, variation of pH is used to evaluate the changes of components during hydration. Furthermore, CPR can be applied to measure pH of high-dose pulverized fuel ash blending systems, the non-pure cement with slightly lower alkalinity.

Two new iridoids and triterpenoid analogues from the leaves of Viburnum chingii and their anti-acetylcholinesterase activity.

Two undescribed split-ring iridoids (1-2) with six known triterpenes (3-8) and one steride (9) were isolated from the Viburnum chingii. Compound 2 possessed an unprecedented split-ring iridoid skeleton formed by electrocyclic reaction and split ring. The structures and absolute configurations of the new iridoids were established by NMR, HRESIMS, and ECD calculations. All the isolated compounds were tested for AChE inhibitory activity. Biologically, 1, 2, 3, 4, and 7 displayed significant AChE effects compared to the positive control donepezil, and have also been subjected to molecular docking studies.

HSQC-based small molecule accurate recognition technology discovery of diverse cytotoxic sesquiterpenoids from Elephantopus tomentosus L. and structural revision of molephantins A and B.

Elephantopus tomentosus L. is a perennial herb taxonomically belonging to the family Asteraceae, which has been used as a folk medicine for the treatment of hepatobiliary diseases. Sesquiterpenoids from this plant have broad biological activities, including anti-tumor, anti-inflammatory, and antibacterial effects. In this study, fifteen structurally diverse sesquiterpenoids comprised 11 germacrane-type and 4 eudesmane-type sesquiterpenoids were prioritized to isolated from Elephantopus tomentosus L. based on the HSQC-based Small Molecule Accurate Recognition Technology (SMART) strategy. Among them, ten sesquiterpenoids were previously unreported, and their structures were elucidated by spectroscopic data, computational methods, single-crystal X-ray diffraction crystallographic data or electronic circular dichroism calculations. In addition, the structures of two known sesquiterpenoids, molephantin A and B, which were reported to possess E-geometry for the Δ1(10) double bond, were revised by reanalyzing their spectroscopic and X-ray crystallographic data. Some sesquiterpenoids exhibited significant cytotoxic activities against Hep3B and HepG2 cell lines.

Chemical constituents from Daphne giraldii and their cytotoxicities and inhibitory activities against acetylcholinesterase.

Seven triterpenoids (1-7), two prenylated coumarins (8 and 9), and one diphenylpropane (10), including five previously undescribed compounds (1-3, 8, and 10), were obtained from the stem and root barks of Daphne giraldii. The structures and absolute configurations of the new triterpenoids were established by NMR, HRESIMS, ECD calculations, and single-crystal X-ray diffraction analysis. All identified compounds were tested for cytotoxicities (human tumour cell line Hep3B) and inhibitory effects on AChE in vitro. Notably, prenylated coumarins (8 and 9) exhibited moderate cytotoxic activities and 3-hydroxy-substituted triterpenoids (2 and 4) showed mild inhibitory effects on AChE. Furthermore, compounds 2 and 4 have also been subjected to molecular docking studies to investigate the inhibitory mechanism.

Chemical structures and anti-tyrosinase activity of the constituents from Elephantopus scaber L.

Four undescribed compounds including one germacrane-type sesquiterpene lactones (1), alkaloid (2) along with two neolignans (3-4) were isolated from Elephantopus scaber L. Their structures and absolute configurations were elucidated unambiguously by means of 1D and 2D NMR spectroscopic data analysis, and quantum chemical electronic circular dichroism calculations, as well as single-crystal X-ray crystallography. Their anti-tyrosinase activities have been evaluated in vitro and compound 2 exhibited significant inhibitory activity. Furthermore, molecular docking was performed to study the interaction patterns between 2 and the tyrosinase.

Insight into Isolation and Characterization of Phenolic Compounds from Hawthorn (Crataegus pinnatifida Bge.) with Antioxidant, Anti-Acetylcholinesterase, and Neuroprotective Activities.

Recent epidemiologic studies have demonstrated a link between the consumption of daily functional fruits rich in phenols and the prevention of disease for neurodegenerative disorders. Hawthorn products are derived from the functional fruit hawthorn, which is rich in phenols and has been used around the world for centuries. In order to explore the phenolic components in hawthorn, the investigation of the ethanol extract led to the separation of five new phenol compounds (1a/1b, 2-4), including one pair of enantiomers (1a/1b), along with seven disclosed analogs (5-11). Their structures were elucidated based on extensive spectroscopic analyses and electronic circular dichroism (ECD). The compounds (1-11) were tested for antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS), and ferric reducing antioxidant power (FRAP) methods. Apart from that, monomeric compounds 2, 4, and 6 exhibited more potent protective capabilities against H2O2 (hydrogen peroxide)-induced SH-SY5Y cells. Meanwhile, electronic analyses were performed using the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) to analyze compounds 2, 4, and 6. Furthermore, compounds (1-11) measured acetylcholinesterase (AChE) inhibitory activities, and 2, 4, and 6 possessed greater AChE inhibitory activity than donepezil. At the same time, molecular docking was used to investigate the possible mechanism of the interaction between active compounds (2, 4, and 6) and AChE.

Study on the biogas potential of anaerobic digestion of coffee husks wastes in Ethiopia.

The poorly controlled discharge of coffee husks in Ethiopia causes severe environmental pollution and is a waste of resources. The volatile solid and carbon content in coffee husks waste indicates that it is rich in organic matter and has huge potential to produce biogas. This study investigated the feasibility of coffee husks to produce biomass through anaerobic digestion, based on temperature, initial pH, inoculum/substrate (I/S) ratio and carbon/nitrogen (C/N) ratio. The study demonstrated that the maximum production of biogas and methane reached 3359.6 ml and 2127.30 ml, respectively, under the conditions of mesophilic temperature (35±1°C), an initial pH of 7, an I/S ratio of 0.75 and a C/N ratio of 30. Based on this result, the effects of trace elements (Fe2+, Ni2+, Co2+) on biogas production and methane content were also explored. Compared with the group with no addition of trace elements, the experiment adding trace elements had significant enhancement effects on the production of biogas and methane, in which Fe2+ played a leading role (p<0.05). Fe2+ promoted the hydrolysis and acidification of coffee husks, resulting in the production of a series of intermediates such as volatile fatty acids and the other kinds of dissolved organic matter. Furthermore, the cooperation of Ni2+, Co2+ and Fe2+ enhanced the activity of the enzyme system in methanogens, promoting methane production. The results in this paper show that coffee husks have clear biogas potential through anaerobic digestion, and its effective utilization could fulfill the dual purpose of solid waste reclamation and local environmental protection in Ethiopia.

Rapid nitrogen fixation contributes to a similar growth and photosynthetic rate of Robinia pseudoacacia supplied with different levels of nitrogen.

Robinia pseudoacacia L. is a legume species that is widely used in afforestation, which has high N2 fixation capacity and rapid growth rate. Both nitrogen (N) supply and phenology affect plant growth, photosynthesis and leaf senescence. The aim of this study was to determine how N supply affects N2 fixation, leaf photosynthesis and senescence of R. pseudoacacia at different phenological stages. Seedlings of R. pseudoacacia were supplied with different levels of 15N-labelled NH4NO3 solution, with seedlings of Sophora japonica Linn. as reference plants to calculate the percentage of N derived from the atmospheric N2 (%Ndfa). Compared with plants supplied with a high N level, those with a low N supply had a higher %Ndfa at an early developmental stage. Nitrogen fixation compensated the effect of a low N supply on plant growth in R. pseudoacacia. A high N supply decreased biomass allocation to lateral roots and nodules, and increased the relative growth rate of plant height as well as specific leaf area. The eighth mature compound leaf of R. pseudoacacia tended to have a higher net photosynthetic rate than the fourth leaf, and the leaves still maintained a moderate photosynthetic rate in early autumn. Plants tended to allocate more biomass to leaves at an early developmental stage and to stems and roots at a later developmental stage (3 months old). The N level did not affect leaf photosynthesis at different phenological stages, primarily due to (i) a high %Ndfa under low N supply at early growing stage, and a similar high %Ndfa under all N supplies at a late growing stage, and (ii) the delayed greening phenotype of expanding leaves to save nutrients for mature leaves.

Matrine Inhibitory Effect on Self-renewal and Re-sensitization of 5-FU Resistant NSCLC Stem Cells were through Let-7b dependent Downregulation of CCND1.

Matrine is one of the major alkaloids extracted from Sophora flavescens Ait of the traditional Chinese medicine, was the main chemical ingredient of compounds of Kushen injection. The Matrine is considered as a promising therapeutic agent for curing nonsmall cell lung cancer (NSCLC), used either alone or combined with chemotherapeutic agents. In the present study, we focused on the possible roles of Matrine exerted on the self-renewal ability of stem-like cells of the NSCLC group, as well as the cytotoxicity of chemotherapeutic agents, in vitro and in vivo. Here we reported that Matrine inhibits cancer stem-like cell (CSC) properties through upregulation of Let-7b and suppression of the Wnt pathway. Overexpression of Let-7b suppressed the ability of tumorsphere formation, decreased Wnt pathway activation through inhibiting its transcriptional activity in lung CSCs. Further studies revealed that Let-7b directly targeted CCND1 and decreased its expression, whereas Matrine increased Let-7b levels and followed by inactivation of the CCND1/Wnt signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in lung CSCs. What is more, we found that Matrine increased Let-7b level in an endoribonuclease DICER1-dependent manner. And xenografts in nude mice evidenced that Matrine increased the sensitivity of lung CSCs to 5-FU and inhibited the accumulation of CCND1 in tumor tissues induced by 5-FU. Taken together, these data illustrate the role of Let-7b in regulating lung CSCs traits and DICER1/let-7/CCND1 axis in Matrine or in combination with 5-FU intervention of lung CSCs' expansion, helping to fulfill the anti-cancer action of Matrine.

Antimicrobial Activity of an Implantable Wireless Blue Light-Emitting Diode Against Root Canal Biofilm In Vitro.

Objective: We developed an implantable wireless blue micro light-emitting diode (micro-LED) device and evaluated the utility of continuous antimicrobial blue light (aBL) irradiation emitted from this micro-LED for root canal disinfection. Methods: An implantable wireless blue micro-LED device (peak wavelength: 410 nm, maximum power: 15 mW) was developed to be placed in the root canal. Optical transmission of the device in human dentin tissue was simulated using Monte Carlo ray-tracing method. The bactericidal effect of low-level aBL on planktonic root canal infection-related bacteria [Enterococcus faecalis, methicillin-resistant Streptococcus aureus (MRSA), and Prevotella intermedia] was evaluated by colony counting. The biocompatibility of continuous low-level aBL exposure was evaluated by infrared thermal imaging and cell viability tests. Thirty extracted intact human single-rooted teeth were prepared and the root canals were infected with E. faecalis for 14 days to form biofilm. The infected root canals were randomly divided into three groups (n = 10), and treated with normal saline (group NS), calcium hydroxide (group CH), and micro-LED device (group aBL) for 3 and 7 days. The bactericidal effect of each group was evaluated by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Results: Monte Carlo simulation showed that blue light irradiation of the micro-LED device decreased exponentially with the light transmission distance through human dentin tissue. Planktonic E. faecalis, MRSA, and P. intermedia were significantly eliminated after irradiation with 432, 36, and 1.35 J/cm2 aBL, respectively (p < 0.05). Infrared thermal imaging and cell viability tests showed that continuous aBL exposure is biocompatible in vitro. CLSM and SEM analyses revealed that the micro-LED device had a greater antimicrobial effect than CH on E. faecalis biofilm in the root canal. Conclusions: The wireless blue micro-LED device is a promising and user-friendly approach for root canal disinfection that will facilitate infection control in the root canal using aBL.

Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points.

The aim of this study was to determine the effects of acupotomy on energy crises in rat trigger points (TrPs) by measuring mechanical pain thresholds (MPTs) and levels of acetylcholinesterase (AChE), free sarcoplasmic calcium (Ca2+), adenosine 5'-triphosphate (ATP), adenosine 5'-monophosphate (AMP), substance P (SP), and calcitonin gene-related peptide (CGRP) in rat muscle TrP tissue. Male Sprague Dawley rats (n = 32) were randomly divided into four groups: control, TrP, acupotomy, and lidocaine injection. Enzyme-linked immunosorbent assays were used to measure AChE, and free sarcoplasmic Ca2+ concentrations were determined by fluorescent staining with Fura-2 AM; high-performance liquid chromatography was used to measure ATP and AMP, and SP and CGRP were evaluated by immunohistochemistry. Compared with the control group, free sarcoplasmic Ca2+, AMP, SP, and CGRP were higher in the model group, while MPT, AChE, and ATP were lower. Treatment with acupotomy or lidocaine injection reduced free sarcoplasmic Ca2+, SP, and CGRP and increased MPTs and AChE levels compared with the model group. However, only acupotomy also led to decreased AMP and increased ATP levels relative to the model group. We conclude that acupotomy can alleviate energy crises at TrPs.

Growth and physiological responses to successional water deficit and recovery in four warm-temperate woody species.

Plant responses to drought and their subsequent rehydration can provide evidence for forest dynamics within the context of climate change. In this study, the seedlings of two native species (Vitex negundo var. heterophylla, Quercus acutissima) and two exotic species (Robinia pseudoacacia, Amorpha fruticosa) to China were selected in a greenhouse experiment. The gas exchange, stem hydraulic parameters, plant osmoprotectant contents and antioxidant activities of the seedlings that were subjected to sustained drought and rehydration (test group) as well as those of well-irrigated seedlings (control group) were measured. The two native species exhibited a greater degree of isohydry with drought because they limited the stomatal opening timely from the onset of the drought. However, the two exotic species showed a more 'water spender'-like strategy with R. pseudoacacia showing anisohydric responses and A. fruticosa showing isohydrodynamic responses to drought. Severe drought significantly decreased the leaf gas exchange rates and hydraulic properties, whereas the instantaneous water use efficiency and osmoprotectant contents increased markedly. Most of the physiological parameters recovered rapidly after mild drought rehydration, but the water potential and/or supply of nonstructural carbohydrates did not recover after severe drought rehydration. The results demonstrate that the xylem hydraulic conductivity and shoot water potential jointly play a crucial role in the drought recovery of woody plants. In brief, the native species may play a dominant role in the future in warm-temperate forests because they employ a better balance between carbon gain and water loss than the alien species under extreme drought conditions.

Correction: Acupuncture with reinforcing and reducing twirling manipulation inhibits hippocampal neuronal apoptosis in spontaneously hypertensive rats.

[This corrects the article on p. 770 in vol. 12, PMID: 28616034.].

Acupuncture with reinforcing and reducing twirling manipulation inhibits hippocampal neuronal apoptosis in spontaneously hypertensive rats.

To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats (SHRs), this study used the reinforcing twirling method (1.5-2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method (1.5-2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method (1.5-2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong (LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax mRNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax mRNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR.

An Efficient Method for the Preparative Isolation and Purification of Flavonoid Glycosides and Caffeoylquinic Acid Derivatives from Leaves of Lonicera japonica Thunb. Using High Speed Counter-Current Chromatography (HSCCC) and Prep-HPLC Guided by DPPH-HPLC Experiments.

In this work, the n-butanol extract from leaves of Lonicera japonica Thunb. (L. japonica) was reacted with DPPH and subjected to a HPLC analysis for the guided screening antioxidants (DPPH-HPLC experiments). Then, nine antioxidants, including flavonoid glycosides and caffeoylquinic acid derivatives, were isolated and purified from leaves of L. japonica using high speed counter-current chromatography (HSCCC) and prep-HPLC. The n-butanol extract was firstly isolated by HSCCC using methyl tert-butyl ether/n-butanol/acetonitrile/water (0.5% acetic acid) (2:2:1:5, v/v), yielding five fractions F1, F2 (rhoifolin), F3 (luteoloside), F4 and F5 (collected from the column after the separation). The sub-fractions F1, F4 and F5 were successfully separated by prep-HPLC. Finally, nine compounds, including chlorogenic acid (1), lonicerin (2), rutin (3), rhoifolin (4), luteoloside (5), 3,4-Odicaffeoylquinic acid (6), hyperoside (7), 3,5-O-dicaffeoylquinic acid (8), and 4,5-O-dicaffeoylquinic acid (9) were obtained, respectively, with the purities over 94% as determined by HPLC. The structures were identified by electrospray ionization mass spectrometry (ESI-MS), 1H- and 13C-NMR. Antioxidant activities were tested, and the isolated compounds showed strong antioxidant activities.

Sleep and Cognitive Abnormalities in Acute Minor Thalamic Infarction.

In order to characterize sleep and the cognitive patterns in patients with acute minor thalamic infarction (AMTI), we enrolled 27 patients with AMTI and 12 matched healthy individuals. Questionnaires about sleep and cognition as well as polysomnography (PSG) were performed on days 14 and 90 post-stroke. Compared to healthy controls, in patients with AMTI, hyposomnia was more prevalent; sleep architecture was disrupted as indicated by decreased sleep efficiency, increased sleep latency, and decreased non-rapid eye movement sleep stages 2 and 3; more sleep-related breathing disorders occurred; and cognitive functions were worse, especially memory. While sleep apnea and long-delay memory recovered to a large extent in the patients, other sleep and cognitive function deficit often persisted. Patients with AMTI are at an increased risk for hyposomnia, sleep structure disturbance, sleep apnea, and memory deficits. Although these abnormalities improved over time, the slow and incomplete improvement suggest that early management should be considered in these patients.

Functional traits contributed to the superior performance of the exotic species Robinia pseudoacacia: a comparison with the native tree Sophora japonica.

Functional traits determine the ecological strategies of plants and therefore are widely considered to feature in the success of invasive species. By comparing a widespread exotic invasive species Robinia pseudoacacia L. with a related native one Sophora japonica L., this research aimed to study strategies of R. pseudoacacia for superior performance from the perspective of functional traits. We conducted a greenhouse experiment in which seedlings of R. pseudoacacia and S. japonica were grown separately under a factorial combination of two light regimes and three levels of nitrogen (N) fertilization, including a control and two levels intended to represent ambient and future levels of N deposition in Chinese forests. After 90 days of treatment, performance and functional traits were determined for the two species, the former referred to as the total biomass (TB) that directly affected fitness. Trait plasticity and integration (the pattern and extent of functional covariance among different plant traits) were analyzed and compared. We found that the two species showed significantly different plastic responses to light increase: in the low-light regime, they were similar in performance and functional traits, while in the high-light regime, R. pseudoacacia achieved a significantly higher TB and a suite of divergent but advantageous functional traits versus S. japonica, such as significantly greater photosynthetic capacity and leaf N concentration, and lower carbon-to-N ratio and root-to-shoot ratio, which conferred it the greater performance. Moreover, across the light gradient, R. pseudoacacia showed higher correlations between photosynthetic capacity and other functional traits than S. japonica. In contrast, N deposition showed little impact on our experiment. Our results suggested that across light regimes, three aspects of functional traits contributed to the superior performance of R. pseudoacacia: functional trait divergence, significantly different plasticity of these traits, as well as greater overall trait coordination.

Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.

CONTEXT: Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis. OBJECTIVES: Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2. SETTING: The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China. OUTCOME MEASURES: The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor ß-1 (TGF-ß1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-ß (IL-1ß), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver. RESULTS: The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-ß1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes induced by CCl4. The cell culture also showed that CCl4 elevated the levels of inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment partially reversed the changes induced by CCl4. CONCLUSIONS: GSPB2 had hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats and inhibited the inflammatory response and oxidative stress in vivo and in vitro.