The compatibility rationality of Sijunzi decoction based on integrated analysis of tissue distribution and excretion characteristics in spleen deficiency syndrome rats.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classical prescription for treating spleen deficiency syndrome (SDS), Sijunzi decoction (SJZD) is composed of Ginseng Radix et Rhizoma (RG, Panax ginseng C.A.Mey.), Atractylodes Macrocephalae Rhizoma (AM, Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf) and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle (GRP, processed from Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L.). The non-polysaccharides (NPSs) are the pharmacodynamic substance basis of SJZD, whose pharmacokinetics in SDS rats were elaborated previously. Further study on their tissue distribution and excretion properties is of significance for understanding the compatibility laws of SJZD. AIM OF THE STUDY: The aim was to unravel the tissue distribution and excretion characteristics of NPSs of SJZD in SDS rats, and explore the scientific connotation of SJZD compatibility. MATERIALS AND METHODS: A validated ultrafast liquid chromatography tandem mass spectrometry method was developed for monitoring the accurate dynamics of sixteen components in the tissues, feces and urine of SDS rats. The four incomplete formulae of SJZD were prepared by randomly deleting one herb to uncover the herb-herb interactions. RESULTS: All components of NPSs in SJZD were distributed in the tissues, except for ononin in the heart. Among them, glycyrrhetinic acid and atractylenolide III were more abundant in the liver and lung, respectively, while other components were enriched in the ileum, especially saponins. The evaluation of fecal excretion and urinary excretion revealed the low cumulative excretion of all components. The comparative analysis of incomplete formulae indicated that the tissue distribution and excretion became faster after removing Poria from SJZD, while a lack of RG led to slower tissue distribution. The tissue distribution at most time points was reduced when AM was absent. Further comprehensive visualization implied that SJZD compatibility can improve tissue distribution of the NPSs, especially ginsenosides and atractylenolide, at the specific time periods. CONCLUSION: The tissue distribution and excretion characteristics of NPSs of SJZD were elucidated in current research. Meanwhile, this study proposed new insights into the mechanism of SJZD compatibility rationality.

Deep-fried Atractylodes lancea rhizome alleviates spleen deficiency diarrhea-induced short-chain fatty acid metabolic disorder in mice by remodeling the intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood. AIM OF THE STUDY: The antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora. MATERIALS AND METHODS: The effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin, claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting. SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography-mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR. RESULTS: Treatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis, and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective. CONCLUSION: EEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.

Polysaccharides from Pseudostellaria heterophylla modulate gut microbiota and alleviate syndrome of spleen deficiency in rats.

Pseudostellaria heterophylla, also called Tai-zi-shen (TZS) in Traditional Chinese Medicine (TCM), is always used clinically to treat spleen deficiency symptoms. Polysaccharides in TZS have various pharmacological activities, including anti-diabetic, immune regulation, and myocardial protection. However, the relationship between the spleen-invigorating effects of TZS or its polysaccharides and intestinal flora are not clear. This study investigated the effects of TZS decoction (PHD) and polysaccharide (PHP) on immune function and intestinal flora in a rat model of spleen deficiency syndrome (SDS) induced by a decoction of raw rhubarb (RRD). PHD and PHP increased immune organ index, alleviated inflammatory cell filtration, and reduced the levels of pro-inflammatory cytokines in rats with spleen deficiency syndrome. In addition, the production of butyric acid was promoted in PHD and PHP groups. Moreover, 16S rRNA gene sequencing showed that PHD and PHP reduced the relative abundance of Firmicutes while increasing the one of Bacteroidetes; significantly increased the abundance of Lactobacillus and decreased the abundance of Rombutsia; and PHP significantly increased the abundance of Alloprevotella. And there was a significant positive correlation between the alleviation of SDS and short-chain fatty acids (SCFAs)-producing bacteria. These findings suggested PHD and PHP, especially PHP, has a potential to relieve spleen deficiency by reducing intestinal inflammation, modulating structure and composition of gut microbiota, and promoting the production of butyric acid.

Qihuzha granule attenuated LPS-induced acute spleen injury in mice via Src/MAPK/Stat3 signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qihuzha granule (QHZG), is one of traditional Chinese patent medicines composed of eleven edible medicinal plant, which has been used in the clinic for the treatment of indigestion and anorexia in children caused by deficiency of the spleen and stomach. Yet it is noteworthy that QHZG has therapeutic effect on recurrent respiratory tract infection (RRTI) in children. However, its potential molecular mechanisms remained unclear. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic effect and potential mechanism of QHZG on lipopolysaccharide (LPS) induced acute spleen injury. MATERIALS AND METHODS: The acute spleen injury model was induced by intraperitoneal injection of LPS (10 mg/kg) and safe doses of QHZG was administered by gavage once a day for 23 days before LPS treatment. Serum inflammatory cytokines including interleukin-2 (IL-2), IL-1ß, IFN-γ, and tumor necrosis factor-α (TNF-α) were tested by ELISA. Related protein levels were detected by Western blotting. Hematoxylin-eosin (HE) staining was employed to observe the histological alterations. The distribution of macrophages and neutrophils in the mouse spleen was examined by immunofluorescence analysis. RESULTS: QHZG pretreatment significantly abolished the increased secretion of cytokines such as interleukin-2 (IL-2), IL-1ß, IFN-γ, and tumor necrosis factor-α (TNF-α), which were attributable to LPS treatment. Immunofluorescence staining and Histological analysis of spleen tissue revealed the protective effect of QHZG against LPS-induced acute spleen injury in mice. Further study indicated that pretreatment with QHZG significantly inhibited LPS-induced phosphorylation of Src. Accordingly, the increased phosphorylation of Src downstream components (JNK, ERK, P38 and STAT3) induced by LPS was remarkably diminished by QHZG, suggesting the involvement of Src/MAPK/STAT3 pathway in the inhibitory effects of QHZG on spleen injury in mice. CONCLUSION: Our study demonstrated that QHZG protected mice from LPS-induced acute spleen injury via inhibition of Src/MAPK/Stat3 signal pathway. These results suggested that QHZG might serve as a new drug for the treatment of LPS-stimulated spleen injury.

Metabolomics of Spleen-Yang deficiency syndrome and the therapeutic effect of Fuzi Lizhong pill on regulating endogenous metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Spleen-Yang deficiency (SYD) is one of the primary causes of many digestive diseases, such as ulcerative colitis (UC), and irritable bowel syndrome (IBS), but its endogenous metabolic characteristics are still unclear. Fuzi Lizhong pill (FLZP) is well-known for its powerful capacity for treating SYD; however, its mechanisms require further study. AIM OF THE STUDY: Herein, our present study aimed to investigate the essence of SYD from the perspective of metabolomics, and tried to reveal the anti-SYD action mechanisms of FLZP. MATERIALS AND METHODS: Firstly, the compound factor modeling method with the principle of "indiscipline in diet + excessive fatigue + intragastric administration of Senna water extracts" was used to establish Sprague Dawley (SD) rats as SYD model. Then, the visceral index, motilin (MTL), malonaldehyde (MDA), Interleukin 1 alpha (IL-1α), and Interleukin 6 (IL-6) levels were used to verify the anti-SYD effect of FLZP. In addition, serum samples were analyzed by UPLC-QE/MS metabolomics technique. Finally, the metabolic pathways associated with specific biomarkers were analyzed to research the possible mechanism underlying the action of FLZP. RESULTS: The expression of MTL, MDA, IL-1α, and IL-6 were regulated by FLZP, which suggested that it has relieved diarrhea and gastrointestinal motility disorder caused by SYD and had an anti-peroxidation, anti-inflammatory, and immune regulation effect. A total of 75 metabolites were found to be the potential biomarkers of SYD. Moreover, FLZP regulates 21 metabolites and 10 vital pathways including the tricarboxylic acid (TCA) cycle, sphingolipid metabolism, and histidine metabolism. CONCLUSION: SYD primarily causes disorders of amino acid metabolism, lipid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, nucleotide metabolism, and translation. In addition, FLZP regulated carbohydrate, lipid, and amino acid metabolisms, gastrointestinal motility, digestive juice secretion, immune regulation, as well as antioxidant effects. Hence, FLZP had a good therapeutic effect on treatment of SYD. It might be a promising therapeutic agent for the treatment of SYD-related diseases.

The effects of aqueous extract of Maca on energy metabolism and immunoregulation.

BACKGROUND: In the present work, we investigated the effects of aqueous extract of Maca (AEM) on energy metabolism and immunoregulation in spleen-deficient mice. METHOD: We established a cyclophosphamide-induced spleen-deficiency model with ginseng, a herb that strengthens splenic function, as a control. Sixty male Kunming mice were randomly divided among 5 groups: normal, model, ginseng control (1.5 g/kg), AEM high dose (1.5 g/kg), and AEM low dose (0.75 g/kg). All animals, except those in the normal group, were injected with cyclophosphamide to induce spleen deficiency. Furthermore, we investigated differences in the thermotropic behaviors of mice using the Animal Thermotropism Behavior Surveillance System to detect energy metabolism-related assays and immune regulation assays. RESULTS: Mice given AEM exhibited tropism in response to hot plate exposure. AEM inhibited loss of body weight and immune organ atrophy caused by cyclophosphamide, increased the cAMP/cGMP ratio in blood, and enhanced the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, lactate dehydrogenase, and hepatic glycogen. AEM significantly reversed declining white blood cells and platelet counts, and increased the hemoglobin content within peripheral blood cells. AEM improved the protein levels of IFN-γ, TNF-ß, IL-2, and IL-4 in the spleen. CONCLUSIONS: Maca possesses the Traditional Chinese Medicine (TCM) property of warm and appears to strengthen spleen function.

In Vitro Effects of Ginseng and the Seed of Zizyphus jujuba var. spinosa on Gut Microbiota of Rats with Spleen Deficiency.

Ginseng and the seed of Zizyphus jujuba var. spinosa, which are traditional Chinese medicinal materials, were often used in ancient Chinese recipes as a pair of medicines. They can replenish the primordial qi and tonify the spleen. This study investigated the effects of ginseng and the seed of Zizyphus jujuba var. spinosa (GS) extract on gut microbiota diversity in rats with spleen deficiency syndrome (SDS). A total of 52 compounds (including 16 flavonoids, 35 saponins, and 1 alkaloid) were identified and analyzed from the GS extract by UPLC-Q-Orbitrap-MS/MS. The GS extract significantly increased the relative abundance of Firmicutes and Bacteroidetes in rats with SDS but decreased that of Proteobacteria and Actinobacteria. At the genus level, the GS extract significantly increased the relative abundance of Lactobacillus and Bifidobacterium in rats with SDS but decreased that of Streptococcus, Escherichia-Shigella, Veillonella, and Enterococcus. In addition, the GS extract influenced glucose and amino acid metabolism. In summary, the results showed that the GS extract changed the structure and diversity of gut microbiota in rats with SDS and balanced the metabolic process.

Efficacy and safety of oral traditional Chinese patent medicine in treatment of liver stagnation and spleen deficiency of depression: A protocol for systematic review.

BACKGROUND: Depression is a kind of chronic and recurrent mental disorder, the main clinical characteristics of the patients are marked and persistent depression. At the same time, it is often accompanied by chronic physical disease, cognitive impairment, and functional damage, which is one of the common diseases that seriously threaten human health. At present, 3 kinds of oral Chinese patent medicine have clinical comparability in the treatment of depression of liver stagnation and spleen deficiency, but there is no evidence for clinical efficacy and safety. Therefore, this study aims to integrate the clinical related syndromes of direct and indirect comparison by using systematic evaluation and network meta-analysis (NMA). According to the data, the different Chinese patent medicines with the same evidence body for the treatment of the disease are collected, analyzed, and sequenced in a quantitative and comprehensive way, and then the advantages and disadvantages of the efficacy and safety between different Chinese patent medicines are screened out to get the best choice scheme, thus providing reference value and evidence-based theoretical evidence for the clinical optimization of drug selection. METHODS: Comprehensive retrieval of China National Knowledge Infrastructure, Chinese scientific journal database (VIP), China biological feature database (CBM) and WANFANG Data Chinese electronic database and the Cochrane Library, PubMed, Web of Science, and EMBASE foreign database. Search and publish the clinical randomized controlled trials of these 3 Chinese patent medicines combined with fluoxetine compared with fluoxetine. The retrieval time is from the establishment of the database to October 31, 2019. The 2 first authors will screen the literatures that meet the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane 5.1 manual standard. R and Aggregate Data Drug Information System software were used for data consolidation and NMA to evaluate the ranking probability of all interventions. RESULTS: This result will show that the best oral Chinese patent medicine to assist the treatment of liver stagnation and spleen deficiency depression provides reliable evidence. CONCLUSION: This study will provide systematic evidence-based medicine evidence for TCM assisted treatment of depression of liver stagnation and spleen deficiency type, and help clinicians, patients with depression and decision-makers to make more effective, safer, and economic optimal treatment plan in the decision-making process. PROSPERO REGISTRATION NUMBER: CRD42019115695.

Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency.

Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group；The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4'-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms.

Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I.

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg-1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.

Effect of Zhizhu Kuanzhong capsule on functional dyspepsia: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disorder affecting people in the globe. Spleen-deficiency syndrome is one of its basic syndromes. Zhizhu Kuanzhong capsule was the most frequent Chinese herbal formula used in the spleen-deficiency researches. We aim to assess the effectiveness and safety of Zhizhu Kuanzhong capsule on FD. METHODS: A systematic literature search for randomized controlled trials (RCTs) from their inception until December 31, 2017 will be conducted using 7 databases: PubMed, Cochrane Library, Embase, VIP Database, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese BioMedical Database. Inclusion the trials of Zhizhu Kuanzhong capsule which evaluate motilin level, clinical syndrome, and side effect in people with FD. The primary outcome measures will be motilin level, clinical syndrome integral, and clinical total effective rate. Data extraction and risk of bias assessments will be performed by 2 reviewers independently. Methodological and reporting quality of included studies will be assessed by the consolidated standards of reporting trials for Chinese herbal medicine formulas. All statistical analyses will be conducted using RevMan V.5.3 software. Funnel plots, Begg's test, and Egger's test will be developed to evaluate reporting bias. RESULTS: This review will assess the effect of Zhizhu Kuanzhong capsule on clinical total effective rate, symptom remission rate, plasma motilin level, and safety of FD in patients. CONCLUSION: The conclusion of our study will provide updated evidence to judge whether Zhizhu Kuanzhong capsule is an effective intervention for patients with FD.

MECHANISMS OF COIX SEED COMPOSITIONS IN THE TREATMENT OF SPLEEN DEFICIENCY AND WET DAMPNESS ZHENG.

BACKGROUND: Coix seed has the functions of fortifying the spleen and inhibiting the dampness. However, it remains unclear which Coix seed compositions is responsible for these functions. Previous investigations have revealed that the main compositions of Coix seed are proteins, polysaccharides, oils and starches. The objectives of this study are to explore which is the most effective compositions in fortifying the spleen and examine how Coix seed works in regulating the water transport on the spleen deficiency and wet dampness (SDWD) rat model. MATERIALS AND METHODS: The rats used were divided into (i) control group, (ii) model group, (iii) decoction group, (iv) protein group, (v) polysaccharide group, (vi) oil group and (vii) starch group. The urine volume, the drinking volume and the water loading index in each group were calculated. Agilent 8*60K array was used for microarray-based gene expression analysis. The differential mRNAs related to the transport activity were screened. qRT-PCR was used to validate the mRNA microarray. RESULTS: The results demonstrated that all treatment groups could decrease the dampness of SDWD rats. mRNA microarray had significant effect on the protein group and the polysaccharide group in regulating the water transport, among which the most significant mRNA was Fabp6, Slc51a, Slc51b, Slc11a2, Slc4a10 and AQP3 respectively. CONCLUSION: The compositions of proteins and polysaccharides had the most significant effect in regulating the water transport of SDWD rat model. The contributing mRNA focused on Fabp, Slc and AQP family.

Java brucea and Chinese herbal medicine for the treatment of cholesterol granuloma in the suprasellar and sellar regions: A case report and literature review.

RATIONALE: A cholesterol granuloma (CG) is usually found in the middle ear, papilla, orbits, petrous apex, and choroid plexus, but is highly uncommon in the skull. In spite of benign clinicopathological lesions, bone erosion can be seen occasionally in the patient with CG. The optimal treatment strategy is radical surgery, but complete excision is usually impossible due to anatomical restrictions and a risk of injury to the key structures located nearby. Here, we report a patient with CGs in the suprasellar and sellar regions who was successfully treated with Java brucea and Chinese herbal medicine. PATIENT CONCERNS: A 31-year-old man presenting with progressive decreased vision in both eyes was analyzed. DIAGNOSES: A skull magnetic resonance imaging (MRI) scan showed a low-density tumor in the uprasellar and sellar regions and histopathological examination revealed a CG. INTERVENTIONS: The patient was referred the surgery and radiotherapy. In the meantime, brucea soft capsules and herbal medicine combined were administered to him. OUTCOMES: The related clinical symptoms and signs resolved significantly after several months, as his therapy progressed. The patient showed no sign of recurrence during the treatment period. Furthermore, he was still alive and disease-free at 37 months of follow-up visit. LESSONS: Overall, brucea soft capsules and a Chinese herbal formula treatment combined could be beneficial in improving the patient's quality of life with CG in the skull.

[Effect of Jingui Shenqi pill combined with nifedipine for the treatment of elderly hypertensive patients with spleen-kidney Yang deficiency syndrome].

Totally 96 elderly patients with spleen-kidney Yang deficiency type hypertension were selected in this study. Patients were randomly divided into study and control group. It was treated with the Jingui Shenqi pill combined nifedipine sustained-release tablets in the study group and only nifedipine sustained-release tablets for the control group. Meanwhile, the clinical features including reducing blood pressure, blood lipid and traditional Chinese medicine (TCM) syndromes of the two groups were observed pre and post treatment. Finally, the results showed that it could significantly reduce the hypertensive, hyperlipidemia and TCM syndromes in the study group compared with the control group (P < 0.05), which indicated that the combination of the Jingui Shenqi pill with nifedipine sustained-release tablets was effective for the patients with hypertension with spleen-kidney Yang deficiency type, especially for decreasing TCM syndromes and the blood lipid.

[Study on interference effect of Sijunzi decoction on brain-gut CaM/CaMK II of spleen Qi deficiency syndrome rats].

OBJECTIVE: To observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction. METHOD: Male Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed. RESULT: Spleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01). CONCLUSION: The formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.

Effects of dietary selenium on histopathological changes and T cells of spleen in broilers exposed to aflatoxin B1.

Aflatoxin B1 (AFB1), which causes hepatocellular carcinoma and immune-suppression, is commonly found in feedstuffs. To evaluate the ability of selenium (Se) to counteract the deleterious effects of AFB1, two hundred 1-day-old male avian broilers, divided into five groups, were fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.3 mg/kg AFB1+0.2 mg/kg Se (+Se group I), 0.3 mg/kg AFB1+0.4 mg/kg Se (+Se group II) and 0.3 mg/kg AFB1+0.6 mg/kg Se (+Se group III), respectively. Compared with control group, the relative weight of spleen in the AFB1 group was decreased at 21 days of age. The relative weight of spleen in the three +Se groups was higher than that in the AFB1 group. By pathological observation, the major spleen lesions included congestion in red pulp and vacuoles appeared in the lymphatic nodules and periarterial lymphatic sheath in the AFB1 group. In +Se groups II and III, the incidence of major splenic lesions was decreased. The percentages of CD3+, CD3+CD4+ and CD3+CD8+ T cells in the AFB1 group were lower than those in control group from 7 to 21 days of age, while there was a marked increase in the three +Se groups compared to the AFB1 group. The results indicated that sodium selenite could improve the cellular immune function impaired by AFB1 through increasing the relative weight of spleen and percentages of splenic T cell subsets, and alleviating histopathological spleen damage.

Effects of Sisheng Decoction on the immunity and anti-stress function in mice with spleen deficiency syndrome.

OBJECTIVE: To study the possible mechanism of Sisheng Decoction on spleen deficiency syndrome via the observation of general conditions, immunity and anti-stress function in Dahuang (Radix et Rhizoma Rhei Palmati)-induced mice model. METHODS: Mice were randomized and grouped based on the body weight. The establishment of model and the treatment were done simultaneously. Except the mice in normal group, the decoction and the Dahuang powder were separately given in the morning and the afternoon for 14 d. The general condition of the mice, the rectal temperature, the time of burden swimming, the indexes of thymus and spleen and the interleukin-2 (IL-2) concentration in the serum were observed. RESULTS: The group treated with Sisheng Decoction showed better performance than that of the model group, including less stool, strong appetite and fast growth; the medium- and high-dose Sisheng Decoction increased the rectal temperature of mice. There was no statistical difference in the thymus and spleen indexes between the groups treated by Sisheng Decoction and the normal group (P>0.05). The thymus index in groups treated by sisheng Decoction was significantly elevated as compared with the model group (P<0.05). The medium- and high-dose Sisheng Decoction significantly improved the concentration of IL-2 and prolonged the time of burden swimming, as compared to the model group (P<0.05). CONCLUSION: The medium- and high-dose Sisheng Decoction is good at invigorating spleen and replenishing qi. One of the possible mechanisms may be related with the improvement of the immunity and anti-stress function of the body.

[Effect of sijunzi decoction on salivary amylase secretion disorder and VIP-cAMP signaling pathway in splenasthenic rats].

OBJECTIVE: To observe the effect of Sijunzi Decoction on secretion disorder of salivary amylase in splenasthenic rat and its mechanism. METHODS: The model group rats received reserpine 0.5 mg/kg through subcutaneous injection while the control group rats received the same volume of saline for 8 days. After being modeled, the model group were divided into treatment group and model control group, treatment group were given orally Sijunzi Decoction, model control group and normal group were fed the same amount of distilled water for 4 weeks. The animal were anaesthetized and the left parotid was removed, the wounds were sutured. When the animals were awake but drowsy, 20 microL 10% glacial acetic acid was applied on the apex of the tongue once a minute for 30 minutes, removed the right parotid gland of the animals. The samples were frozen and amylase activity and VIP, cyclic adenosine monophosphate (cAMP) content and VAMP-8, SNAP-23 protein expression in the parotid glands were detected. RESULTS: Change of sAA in parotid acinar was not significantly different between treatment group and normal groups, but higher in model control groups after acid stimulation. The VIP and PKA contents were not significantly different among three groups. VIP, cAMP content and PKA activity increased significantly in normal group while VIP increased slightly, cAMP and PKA activity decreased in model control groups, which returned to some degrees in treatment group after acid stimulation. Expression of VAMP-8 protein was not significantly different between treatment group and model control groups, while expression of SNAP-23 was lower in model control groups, expression of VAMP-8 and SNAP-23 was higher in treatment group than which in model control groups. CONCLUSION: Sijunzi Decoction has a certain effect on secretion disorder of salivary amylase in splenasthenic rat, which mechanism may be related to recover changes of VIP-cAMP signal pathway in the splenasthenic rat's parotid gland cells,including increase VIP content and expression of VAMP-8 and SNAP-23.

[Clinical study on intervention of spleen-restoring decoction integrating with dormancy hygiene education on subhealthy insomnia of deficiency of both heart and spleen pattern].

OBJECTIVE: To appraise the clinical efficacy, safety and compliance of the intervention of spleen-restoring decoction combined with dormancy hygiene education and the intervention of spleen-restoring decoction alone on sub-healthy insomnia of deficiency of both the heart and spleen pattern. METHOD: Study design took multi-centers, blind and randomized control trial, 107 participants with sub-healthy insomnia of deficiency of both the heart and spleen pattern were assigned to A group (52 cases) which was treated with the intervention of spleen-restoring decoction combined with dormancy hygiene education and B group (55 cases) which was treated with the intervention of spleen-restoring decoction single, compared by efficacy, PSQI score, CGI score, WHOQOL-BREF score and security. RESULT: The efficacy of two group was 79.58%. There was no significant different between them. The PSQI scores before treatment was (11.80 +/- 2.08) and which afer treatment was (6.78 +/- 2.84) of A group. The PSQI scores before treatment was (11.61 +/- 2.00) and which afer treatment was (6.73 +/- 2.27) of B group. There was significant difference in PSQI scores both A group and B group after treatment (P < 0.01); the results of CGI score and WHOQOL-BREF score before and after measurement showed the same as PSQI. There were no significant difference between two groups in all scores after treatment and there was no interaction between time pots and treatment factors . Withdrawal reaction analysis: comparing CGI after withdraw 2 weeks and at the end of treatment course, there was no significant difference between two groups. The same result was in comparison among groups. CONCLUSION: Both the intervention of spleen-restoring decoction integrating with dormancy hygiene education and spleen-restoring decoction had obvious clinical efficacy on treating subhealthy insomnia of deficiency of both the heart and spleen pattern, and had high compliance and safety. The intervention of spleen-restoring decoction integrating with dormancy hygiene education showed no better clinical efficacy than spleen-restoring decoction did.

To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome: a randomized group sequential comparative trial.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine--two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome. METHODS: A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT). RESULTS: A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided p-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.No adverse events were observed in the two groups. CONCLUSIONS: Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485.