The effect of ginsenosides on liver injury in preclinical studies: a systematic review and meta-analysis.

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported. Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis. Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity. Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.

[Virtual screening and antiepileptic activity evaluation of COX-2 inhibitory components in Trachelospermi Caulisetfolium].

This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.

Spatial Heterojunction in Nanostructured TiO2 and Its Cascade Effect for Efficient Photocatalysis.

A highly efficient photoenergy conversion is strongly dependent on the cumulative cascade efficiency of the photogenerated carriers. Spatial heterojunctions are critical to directed charge transfer and, thus, attractive but still a challenge. Here, a spatially ternary titanium-defected TiO2@carbon quantum dots@reduced graphene oxide (denoted as VTi@CQDs@rGO) in one system is shown to demonstrate a cascade effect of charges and significant performances regarding the photocurrent, the apparent quantum yield, and photocatalysis such as H2 production from water splitting and CO2 reduction. A key aspect in the construction is the technologically irrational junction of Ti-vacancies and nanocarbons for the spatially inside-out heterojunction. The new "spatial heterojunctions" concept, characteristics, mechanism, and extension are proposed at an atomic-/nanoscale to clarify the generation of rational heterojunctions as well as the cascade electron transfer.

Interfacial co-existence of oxygen and titanium vacancies in nanostructured TiO2 for enhancement of carrier transport.

The interfacial co-existence of oxygen and metal vacancies in metal oxide semiconductors and their highly efficient carrier transport have rarely been reported. This work reports on the co-existence of oxygen and titanium vacancies at the interface between TiO2 and rGO via a simple two-step calcination treatment. Experimental measurements show that the oxygen and titanium vacancies are formed under 550 °C/Ar and 350 °C/air calcination conditions, respectively. These oxygen and titanium vacancies significantly enhance the transport of interfacial carriers, and thus greatly improve the photocurrent performances, the apparent quantum yield, and photocatalysis such as photocatalytic H2 production from water-splitting, photocatalytic CO2 reduction and photo-electrochemical anticorrosion of metals. A new "interfacial co-existence of oxygen and titanium vacancies" phenomenon, and its characteristics and mechanism are proposed at the atomic-/nanoscale to clarify the generation of oxygen and titanium vacancies as well as the interfacial carrier transport.

[Electroacupuncture improves intestinal function by down-regulating expression of 5-HT1AR and c-fos proteins in the hypothalamus and colon tissues via brain-gut axis in rats with functional diarrhea].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of 5-HT1A receptor (5-HT1AR) and c-fos proteins in the hypothalamus and colon tissues in functional diarrhea (FD) rats so as to explore its underlying mechanisms in improving intestinal function via brain-gut axis. METHODS: A total of 40 SD rats were randomized into blank control, model, EA Tianshu (ST25)-Dachangshu (BL25, ST25-BL25) and EA Quchi (LI11)- Shangjuxu (ST37, LI11-ST37) groups. The FD model was established by gavage of Folium Sennae (10 mg/kg) and constraint immobilization once daily for 29 days. EA (10 Hz/50 Hz, 1.5 mA) was applied to bilateral ST25 and BL25 in EA ST25-BL25 group, and bilateral LI11 and ST37 in EA LI11-ST37 group for 20 min, once daily for successive 10 days. The expression of 5-HT1AR and c-fos protein in the hypothalamus and colon tissues was determined by using Western blot. The state of stool was recorded for calculating the loose stool rate and diarrhea index. RESULTS: After modeling, the loose stool rate, diarrhea index and expression levels of 5-HT1AR and c-fos proteins in the colon and hypothalamus tissues were obviously increased in the model group in contrast with the blank control group(P<0.01，P<0.05). Following EA intervention, the loose stool rate and diarrhea index, the expression levels of 5-HT1AR and c-fos proteins in the hypothalamus and colon in the EA ST25-BL25 group, and the expression of 5-HT1AR in the colon in the EA LI11-ST37 group were significantly down-regulated relevant to the model group (P<0.01，P<0.05). No significant changes were found in loose stool rate and diarrhea index，and the expression levels of hypothalamic 5-HT1AR and hypothalamic and colonic c-fos proteins in the EA LI11-ST37 group (P>0.05). The expression levels of 5-HT1AR protein in the hypothalamus and c-fos protein in the hypothalamus and colon in the EA LI11-ST37 group were significantly up-regulated relevant to the EA ST25-BL25 group (P<0.05). CONCLUSION: EA of ST25-BL25 can down-regulate expression of 5-HT1AR and c-fos proteins in the hypothalamus and colon tissue in FD rats, which may contribute to its function in improving symptoms of FD possibly via brain-gut axis.

Hippocampal gene expression profiling in a rat model of functional constipation reveals abnormal expression genes associated with cognitive function.

Disease progress and pathological proceeding of functional gastrointestinal disorder (FGID) are considered to be closely related to disordered brain-gut interaction, but only a few researches reported the relationship of functional constipation (FC) and disordered brain-gut interaction. It has been found that FC has a great correlation with emotional problems in clinical patients, but its related mechanisms have not been clearly clarified. In order to explore the molecular pathogenesis of FC related to emotional problem, BGI-500 sequencing technology was used for the first time to study the transcriptomics changes of hippocampus in a rat model. The results showed that the differential expressed genes (DEGs) were mainly involved in the modulation of hemoglobin binding and oxidative stress. These changes could result in changes of hemoglobin content and quality, which could further induce the decreased oxygen-carrying function of erythrocytes. In biological pathway, the disorder of cholinergic system could be speculated through related DEGs. And then, those enriched DEGs were verified by qRTPCR methods As far as the mRNA expressions of Chrna4, Camk2d and Gng13, there were significant difference between the control rats and model rats. These results show that FC could result in side effects on cognitive function, suggesting a new thought for understanding emotional disorder related to cognitive function.

[Effect of "Xiusanzhen" on hippocampal muscarinic cholinergic receptor activity in Alzheimer disease rats].

OBJECTIVE: To explore the effect of "Xiusanzhen" [electroacupuncture (EA) of bilateral "Yingxiang" (LI 20) and "Yintang" (EX-HN 3)] on activities of hippocampal muscarinic cholinergic receptor (mAChR) and the involved neural path in Alzheimer Disease(AD)rats. METHODS: Forty Sprague Dawley rats were randomly divided into normal control, model, olfactory nerve severing (ONS)-EA of "Xiusanzhen" (ONS-EA) and EA of "Xiusanzhen" (EA) groups. AD model was established by intra-hippocampal injection (AP: 3.5 mm, L:2 mm, H: -2.8 mm) of Abeta(1-40) starch-like peptide (10 microg/2 microL) under the aid of a microsyringe installed in a brain stereotaxis instrument. For rats of the ONS-EA group, the olfactory nerve was severed by using a surgical knife after drilling a hole on the skull (5 mm anterior to the bregma, L, R: 2 mm). The mAChR density, and its maximum binding capacity (Bmax) and dissociation constant (Kd) of the hippocampus tissue were measured by using radio-ligand binding analysis and Lowry's microamount protein assay. RESULTS: In comparison with the normal control group, the hippocampal mAChR density and its Bmax in the model group were decreased remarkably (P < 0.05), while the Kd of M-receptor in the model group was increased remarkably (P < 0.05). In comparison with the model group, hippocampal mAChR density and its Bmax in the EA group were up-regulated obviously (P < 0.05), while the Kd of mAChR in the EA group was down-regulated significantly (P < 0.05). No significant differences were found between the model and ONS-EA groups in mAChR density and its Bmax and Kd (P > 0.05). CONCLUSION: "Xiusanzhen"-EA can effectively up-regulate hippocampal mAChR density and Bmax and down-regulate Kd of M-receptor of hippocampus in AD rats, which is dependent on the intact olfactory nerve pathway.

Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer's disease rat.

OBJECTIVE: To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat. METHODS: Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected. RESULTS: Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P < 0.01), with no significant differences between the group C and the group E (P > 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P < 0.01), and SOD and GSH-Px activities significantly decreased (P < 0.01), and brain weight/body weight decreased significantly in the group C (P < 0.01), with no significant differences between the group C and the group E (P > 0.05). CONCLUSION: Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

[Effect of "Xiusanzhen" on learning-memory ability and hippocampal somatostatin and arginine vesopressin contents in vascular dementia rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Xiusanzhen" [bilateral "Yingxiang" (LI 20) + "Yintang" (GV 29)] on learning-memory ability and hippocampal somatostatin (SS) and arginine vasopressin (AVP) contents in vascular dementia (VD) rats. METHODS: Forty SD rats were randomly divided into control, VD model, VD plus olfactory bulb lesion (OBL, destroyed by electro-coagulation) and EA groups, with 10 cases in each. VD model was established by 4-vessel occlusion. Morris maze tests were conducted for evaluating the rats' learning and memory ability. EA (1-3 mA, 80/100 Hz) was applied to bilateral LI 20 and GV 29 in VD + OBL and EA groups for 10 min, once daily (except Saturdays and Sundays) for 6 weeks. The contents of SS and AVP in hippocampus tissue were measured by radioimmunoassay. RESULTS: In comparison with control group, the average escape latency (AEL) prolonged significantly and the target-platform crossing times (TPCT) decreased remarkably in VD model group (P < 0.01). In comparison with VD model group, the AEL was shortened and TPCT increased remarkably in EA group (P < 0.01). No significant differences were found between VD model and VD + OBL groups in the AEL and the TPCT (P > 0.05). Hippocampal SS and AVP contents in VD model group were significantly lower than those in control group (P < 0.05), while those in EA group were markedly higher than those in VD model group (P < 0.05). No significant differences were found between VD model and VD + OBL groups in SS and AVP contents (P > 0.05). CONCLUSION: EA of "Xiusanzhen" can improve VD rats' learning-memory ability, which may be related to its effects in raising hippocampal SS and AVP contents and to the intact olfactory pathway.

[Effect of "Xiusanzhen" on learning-memory ability and hippocampal ChAT and AChE activity in Alzheimer disease rats].

OBJECTIVE: To explore the effect of "Xiusanzhen" [bilateral "Yingxiang" (LI 20) + "Yintang" (EX-HN 3)] on learning-memory ability and choline acetyl transferase (ChAT) and acetyl cholinesterase (AChE) activity of hippocampus tissue in Alzheimer Disease (AD) rats. METHODS: A total of 40 Sprague Dawley rats were randomly divided into control, AD model, AD + olfactory-bulb lesion (OBL, induced by electrocoagulation method) + EA and "Xiusanzhen" (AD + EA) groups. AD model was established by 4-vessel occlusion. Morris water maze tests were conducted for evaluating the rat's learning-memory ability. The activity of ChAT and AChE of hippocampus tissue was detected by colorimetric method. RESULTS: In comparison with control group, the average escape latency (AEL) prolonged significantly and the target-platform crossing times decreased remarkably in AD model group (P<0.01). In comparison with AD model group, the AEL shortened and the target-platform crossing times increased remarkably in AD + EA group (P<0.01). No significant differences were found between AD model and AD + OBL + EA groups in AEL and the target-platform crossing times (P>0.05). The ChAT and AChE activity of hippocampus in AD model group was significantly lower than that of control group (P<0.05), while that of ChAT and AChE in AD + EA group was significantly higher than that in AD model group (P<0.05). No significant difference was found between AD model and AD + OBL + EA groups in ChAT and AChE activity of hippocampus (P>0.05). CONCLUSION: EA of "Xiusanzhen" can markedly raise the learning-memory ability in AD rats, which may be related to its effect in increasing the ChAT and AChE activity of hippocampus in AD rats. Its therapeutical effect also depends on the intact of the olfactory pathway.

[Clinical investigation on electroacupuncture treatment of vascular dementia with "Xiusanzhen"].

OBJECTIVE: To observe the effect of electroacupuncture (EA) in the treatment of vascular dementia (VD) so as to explore an effective therapy for it. METHODS: Sixty cases of VD were randomly divided into acupuncture group and medication (Duxil, 40 mg/time, 2 times/d for 10 weeks) group, with 30 cases in each group. "Xiusanzhen" means that two acupuncture needles were penetrated subcutaneously from bilateral Yingxiang (LI 20) to Shangyingxiang (EX-HN 8) respectively, and the 3rd needle was penetrated from the midpoint between two Yangbai (GB 14) through Yintang (EX-HN 3) to the nasal root, followed by applying EA stimulation to the acupoints. Hasegawa's Dementia Scale (HDS), Mini-mental state examination (MMSE), and Functional Activities Questionnaire (FAQ) were used for assessment of the VD patient's state before and after the treatment. RESULTS: After the treatment, the total effective rates of acupuncture and medication groups were 80.00% and 73.33% respectively. The effective rate of acupuncture group was significantly superior to that of medication group (P<0.05). Before treatment, scores of HDS, MMSE and FAQ in both groups had no significant differences (P>0.05); after the treatment, the scores of HDS and MMSE increased significantly, and that of FAQ decreased remarkably in both groups (P<0.01), and the difference of scores (or absolute value of FAQ) between post-treatment and pre-treatment in EA group was obviously higher than that in medication group (P<0.05). CONCLUSION: Acupuncture of "Xiusanzhen" is effective in the treatment of VD patients.

[Effects of different manipulation methods of acupuncture at Zusanli (ST 36) on signal transduction pathway of STAT5 in human PBMC].

OBJECTIVE: To study on effects of different manipulation methods of acupuncture on the binding ability of signal transducers and activators of transcription (STAT5) in human peripheral blood mononuclear cells (PBMC) with DNA. METHODS: Thirty healthy volunteers were randomly divided into 3 groups; reinforcing method group, reducing method group, normal control group, 10 cases in each group. The expression of STAT5 mRNA and the activation of STAT5 in the human PBMC were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA). RESULTS: In the reinforcing method group, the basic transcription level of STATS mRNA in human PBMC and the binding ability of STAT5 with DNA significantly increased (P<0.01), but in the reducing method group, they did not significantly change as compared with those in the normal control group (P>0.05). CONCLUSION: Cytokines and JAK/STAT signal transduction pathway are in volved in immunoregulative actions of acupuncture of the reinforcing method, but the reasons of influencing the transcription level of STAT5 mRNA and the binding ability of STAT5 with DNA are unclear.