Potential Mechanism of Shenling Baizhusan in Disease Treatment： A Review / 中国实验方剂学杂志

Shenling Baizhusan is a traditional Chinese medicine compound prescription formulated on the basis of Si Junzitang （Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhizae Radix et Rhizoma）. It has excellent functions of replenishing Qi， invigorating spleen， draining dampness， and checking diarrhea， and is one of the classical prescriptions of ''reinforcing earth to generate metal''. This prescription is primarily used in clinical practice to treat malnutrition in children， chronic diarrhea， gastrointestinal dysfunction， and other disorders. In addition， it has a good effect on gastrointestinal adverse reactions associated with radiotherapy and chemotherapy. With the booming of molecular biology， researchers have revealed the role of Shenling Baizhusan in the treatment of diseases， especially the mechanism of regulating different signaling pathways. We retrieved 26 relevant papers （4 written in English and 22 in Chinese） published in recent 5 years from 6 databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Cochrance Library， and Excerpta Medica Database （Embase）. On the basis of these papers， we summarized the mechanisms of Shenling Baizhusan in disease treatment. In the animal model of inflammatory bowel disease， Shenling Baizhusan can protect gastrointestinal mucosa by regulating the activation of nuclear factor kappa-B （NF-κB）， mitogen-activated protein kinase （MAPK）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， and myosin light chain kinase-myosin light chain （MLCK-MLC） signaling pathways. In the animal model of non-alcoholic fatty liver disease， Shenling Baizhusan regulates the activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and Kelch-like ECH-associating protein 1/NF-E2-related factor 2/advanced glycation end-products （KEAP1/NRF2/AREs） signaling pathway， thus alleviating the lipid metabolism disorder induced by high-fat diet and reducing liver lipid accumulation and inflammatory response. In the animal model of lung cancer with bone metastasis， Shenling Baizhusan regulates the activation of PI3K/Akt/mTOR signaling pathway， thus playing an analgesic role. By summarizing the mechanisms of Shenling Baizhusan in treatment of different disease models from signaling pathways， we aim to provide clues for the in-depth study of this prescription.

Effect of ningdong granule on 5-hydroxytryptamine metabolism and 5-HT 2AR of tourette’s syndrome rat models / 国际中医中药杂志

Objective To investigate the effect of Ningdong granule on 5-hydroxytryptamine metabolism and 5-HT2AR of Tourette’s Syndrome(TS) rat models. Methods 32 SD rats were divided into 4 groups randomly, the control group, the model (Apo) group, the low dosage NDG (NGL) group, and the high dosage (NGH) group. TS rat models were induced by intraperitoneal injection (i.p.) with Apo (2 mg/kg) in the experimental groups last 4 weeks. Rats in the control group were injected with normal saline (0.9%) (3 ml/kg, i.p.). Then, the rats were treated by intragastric administration (i.g.) with ND granular at 1.8g/(kg?d)in NGL group, with ND granular at 3.6 g/(kg?d)in NGH group, with distilled water at equal Volume in Control group and Apo group respectively for 12 successive weeks. Analysis the striatum 5-HT2AR protein expression by Immunohistochemical method;Determination of the content of 5-HT and 5-HIAA in striatum by Enzyme linked immunosorbent assay (ELISA). Results The level of 5-HT and 5-HT2AR protein expression in the model group [(1.98±0.14)ng/ml and(143.10±8.01)], compared with the control group[(1.78±0.10)ng/ml and(127.43±6.72)], was up-regulated (P<0.01 or 0.05). The levels of 5-HT and 5-HT2AR protein expression in NGH group[(2.20±0.14)ng/ml and(166.33±9.21)ng/ml] were further up-regulated, and the levels of 5-HIAA in NDH group [(0.58±0.08) ng/ml] became lower, compared with the control group(P<0.01 or 0.05). Conclusion Activity of 5-HT system enhanced in Apo-induced TS rat model. However, the enhanced activity may still be relatively insufficient. The mechanism of ND granulear treating TS was associated with depression of the 5-HT metabolism, up-regulation expression of 5-HT2AR, and improving the activity insufficient of 5-HT system.

Clinical study of Ningdong granule on obsessive-compulsive disorder associated with Tourette's syndrome / 国际中医中药杂志

Objective To investigate the efficacy and safety of Ningdong granule on Obsessive-compulsive disorder (OCD) associated with Tourette's syndrome (TS).Methods Thirty-six patients with OCD associated with TS were randomly divided into 2 groups.18 patients in the treatment group were treated with ND granule,and 18 patients in the control group were treated with fluoxetine,the initial dose of fluoxetine was 10 mg/d,and maximum dose was 60 mg/d.All of the participants with history of medication had to be medication-free for≥ 1 weeks prior to the study.The severity of tics and OCD were evaluated at baseline and at end point (8 w),with Yale Global Tic Severity Scale (YGTSS)and Yale-Brown Obsessive Compulsive Scale (Y-BOCS),the contents of 5-HT in serum were measured by ELISA.Side-effects were evaluated according to an adverse event chart produced by this study team.Results The effective rate of treating tics in treatment group was 88.89％ (16/18),and in control group was 77.78％ (14/18).The effective rate of treating OCD in treatment group was 83.33％ (15/18),and in control group was 88.89％ (16/18).The differences in the aspects between treatment group and control group were not significant (P＞0.05).Compared with YGTSS scores [the treatment group was (27.28 ± 8.10),the control group was (29.17 ± 7.53)] and Y-BOCS scores [the treatment group was (22.72 ± 6.75),the control group was (23.17 ± 6.12)] at baseline,the scores YGTSS scores [the treatment group was (12.72±5.20),the control group was (15.50±5.39)] and Y-BOCS scores [the treatment group was (1250± 4.38),the control group was (12.22±4.31)] of both two groups at end point reduced significantly (P＜0.01),but the difference between the two groups was not significant (P＞0.05).The contents of serum 5-HT in the two groups were significantly raised after treatment [the treatment group was (86.05±24.26 vs 66.00±19.63) ng/ml,P=0.01),the control group was (91.16±26.07 vs 67.52±21.18) ng/ml,P＜0.01].Only one subject reported adverse reactions in the treatment group,while 6 subjects experienced adverse reactions in the control group,but no difference was shown in comparison of the aspect between the treatment group and the control group (P＞0.05).Conclusion ND granule with tiapride could improve the syndrome of tics and OCD associated with TS.ND granule with tiapride and fluoxetine with tiapride showed similar efficacy and safety for OCD with TS.

Apoptosis-inducing effect of cinobufacini on human hepatoma cell line HepG2 and its mechanism of action / 药学学报

To investigate the apoptosis-inducing effect of cinobufacini (Huachansu) on human hepatoma cell line HepG2 and its possible mechanism of action, HepG2 cells were treated with different concentrations of cinobufacini. Cell proliferation was measured by methylthiazolyl tetrazolium (MTT) assay. The morphological changes of apoptosis were observed by Hoechst 33258 staining. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry (FCM). Quantitative real-time RT-PCR and Western blotting analysis were used to detect the mRNA and protein expressions of apoptosis related factors Bcl-2, Bax and p53. The results indicated that cinobufacini could inhibit the proliferation of HepG2 cells in a dose and time dependent manner. Remarkable morphological changes of apoptosis including cytoplasmic and nuclear condensation and partition of cytoplasm were observed by Hoechst 33258 staining. According to FCM analysis, HepG2 cells were arrested in G2/M phase and the apoptotic rate increased with the increase of the concentration of cinobufacini. Both the mRNA and protein expressions of Bax and p53 were up-regulated while Bcl-2 expression down-regulated. Thus, cinobufacini could inhibit the proliferation and induce apoptosis of human hepatoma cell line HepG2. Furthermore, up regulation of Bax and p53 as well as down regulation of Bcl-2 expressions may be one of the important apoptotic inducing mechanisms.

Characteristics of TCM Syndromes in 126 Children with Tourette Syndrome / 中医杂志

Objective To investigate the characteristics of TCM syndromes of Tourette syndrome (TS) to find out the basis for its TCM treatment. Methods Based on the preliminary studies,the TCM syndrome scale of TS is designed to investigate the general data,main symptoms and syndromes of 126 cases of TS children to find out the frequency of each syndrome. Results Of the 126 TS cases,97 were males,accounting for 77%; the average age was 8.31 years; and 32 had a positive family history,accountting for 25.4%. In the tic behavior,the facial twitching and limb twitching occupied 91.6% of the muscular stereotyped tic. In the vocal behavior,the throat and nasal sound occupied 42.1%. In the accompanied symptoms,the inattention occupied 69.8%. In the personality offset,the willfulness occupied 49.2%,irritable hyperactivity occupied 78.6%,and silence occupied 7.1%. More than 50% of the patients had red or dark red tongue with thick or sticky coating. Nearly 70% of them had string-taut or rolling pulse. As for the syndromes,heart-liver deficiency with deficiency wind stirred up,and liver-kidney yin deficiency with yang hyperactivity stirring up wind were common,being 41.3% and 34.1% respectively. Conclusion TS takes the heart-liver deficiency with deficiency wind stirred up and liver-kidney yin deficiency with yang hyperactivity stirring up wind as the common syndromes. The basic treating principle is enriching yin and reducing yang,and smoothing the liver to stop wind. At the same time,reinforcing the spleen and nourishing the heart,and dissolving phlegm and enlightening the brain should be applied for treatment.