MXSGD alleviates CsA-induced hypoimmunity lung injury by regulating microflora metabolism.

Context: Ma Xing Shi Gan Decoction (MXSGD) is a traditional remedy for treating lung injuries that was developed by the Typhoid and Fever School of Pharmaceutical Biology. It has antitussive and expectorant effects, anti-inflammatory, antiviral, regulates the body's immunity, etc. Aim: The aim of this study is to investigate whether MXSGD can ameliorate cyclosporine A (CsA)-induced hypoimmunity lung injury by regulating microflora metabolism. Methods: Establishment of a model for CsA-induced hypoimmunity lung injury. Using 16S rRNA high-throughput sequencing and LC-MS, the effects of MXSGD on gut flora and lung tissue microecology of mice with CsA-induced hypoimmunity were investigated. Results: MXSGD was able to preserve lung tissue morphology and structure, reduce serum inflammatory marker expression and protect against CsA-induced lung tissue damage. Compared to the model, MXSGD increased beneficial gut bacteria: Eubacterium ventriosum group and Eubacterium nodatum group; decreased intestinal pathogens: Rikenellaceae RC9 intestinal group; reduced the abundance of Chryseobacterium and Acinetobacter, promoted the production of Lactobacillus and Streptococcus, and then promoted the lung flora to produce short-chain fatty acids. MXSGD was able to enhance the expression of serum metabolites such as Americine, 2-hydroxyhexadecanoylcarnitine, Emetine, All-trans-decaprenyl diphosphate, Biliverdin-IX-alpha, Hordatin A and N-demethyl mifepristone in the CsA-induced hypoimmunity lung injury model. Conclusion: MXSGD can restore gut and lung microbiota diversity and serum metabolite changes to inhibit inflammation, ameliorate CsA-induced hypoimmunity lung injury.

[Maxing Shigan Decoction improves lung and colon tissue damage caused by influenza virus infection through JAK1/2-STAT1 signaling pathway].

Based on Janus kinase 1/2-signal transducer and activator of transcription 1(JAK1/2-STAT1) signaling pathway, this study explored the immune mechanism of Maxing Shigan Decoction in alleviating the lung tissue and colon tissue damage in mice infected with influenza virus. The influenza virus infection was induced in mice by nasal drip of influenza virus. The normal group, model group, oseltamivir group, antiviral granule group, and Maxing Shigan Decoction group were designed. After intragastric administration of corresponding drugs or normal saline for 3 or 7 days, the body mass was measured, and lung index, spleen index, and thymus index were calculated. Based on hematoxylin-eosin(HE) staining, the pathological changes of lung tissue and colon tissue were observed. Enzyme-linked immunosorbent assay(ELISA) was used to detect serum levels of inflammatory factors interleukin-8(IL-8) and interferon-γ(IFN-γ), Western blot and real-time quantitative polymerase chain reaction(RT-qPCR) to determine the protein and mRNA levels of JAK1, JAK2, STAT1, interferon regulatory factor 9(IRF9), and IFN-γ in lung tissue and colon tissue. The results showed that after 3 and 7 days of administration, the body mass, spleen index, and thymus index were lower(P<0.05 or P<0.01), and the lung index was higher(P<0.01) in the model group than in the normal group. Moreover, the model group showed congestion, edema, and infiltration of a large number of lymphocytes and macrophages in the lung tissue, irregular structure of colon mucosa, ulceration and shedding of epithelial cells, and infiltration of a large number of inflammatory cells. The model group had higher levels of serum IFN-γ(P<0.01), higher protein and mRNA expression of JAK1, JAK2, STAT1, IRF9, IFN-γ in lung tissue(P<0.05 or P<0.01), higher level of JAK2 protein in colon tissue(P<0.01), and higher protein and mRNA levels of STAT1 and IRF9(P<0.05 or P<0.01) than the normal group. Compared with the model group, Maxing Shigan Decoction group had high body mass, spleen index, and thymus index(P<0.05 or P<0.01), low lung index(P<0.05 or P<0.01), and significant alleviation of pathological injury in lung and colon. Moreover, lower serum level of IFN-γ(P<0.05 or P<0.01), protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue(P<0.05 or P<0.01), JAK2 protein level in colon tissue(P<0.01), and protein and mRNA levels of STAT1 and IRF9(P<0.05 or P<0.01) were observed in the Maxing Shigan Decoction group than in the model group. After 3 days of administration, the level of serum IL-8 in the model group was significantly higher than that in the normal group(P<0.01), and the level in the Maxing Shigan Decoction group was significantly reduced(P<0.01). In conclusion, Maxing Shigan Decoction can significantly up-regulate body mass, spleen index, and thymus index, down-regulate lung index, reduce the levels of IL-8 and IFN-γ, and down-regulate protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue and protein and mRNA levels of JAK2, STAT1, and IRF9 in colon tissue, and alleviate pathological damage of lung tissue and colon tissue. The mechanism is the likelihood that it inhibits the activation of JAK1/2-STAT1 signaling pathway to alleviate the damage to lung and colon tissue damage.

Zhuifeng Tougu capsules improve rheumatoid arthritis symptoms in rats by regulating the toll-like receptor 2/4-nuclear factor kappa-B signaling pathway.

OBJECTIVE: To investigate the efficacy of Zhuifeng tougu capsules (, ZFTG) in the treatment of rheumatoid arthritis (RA) in rats and study its mechanism, focusing on the toll-like receptor 2/4-nuclear factor kappa-B (TLR2/4-NF-κB) signaling pathway. METHODS: Type Ⅱ collagen and an artificial climate box were used to construct the rat model of collagen-induced arthritis with wind-cold-dampness arthralgia syndrome. The rats were divided randomly into a control group, wind-cold-dampness syndrome model group, and high-, medium-, and low-dose ZFTG groups. The methotrexate (MTX) control group was treated with the corresponding drug intervention for 28 d. The joint temperature, pain threshold, joint swelling degree, and arthritis index (AI) score were measured. The production of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factors (RFs) in the blood was detected by enzyme-linked immunosorbent assay. The protein expression of TLR2, TLR4, and NF-κB in synovial tissues was detected by Western blotting, and the mRNA expression of TLR2, TLR4, and NF-κB was detected by real-time polymerase chain reaction. RESULTS: Compared with the model group, the joint temperature in each treatment group, the MTX control group, and MTX group recovered, the degree of foot swelling, pain threshold, AI score decreased, serum CRP, ESR, RF level and the levels of TLR2, TLR4, and NF-κB in synovial tissue were decreased (P < 0.05). Among them, the curative effect in the medium-dose and MTX groups was more evident (P < 0.01). CONCLUSION: ZFTG has a significant effect on RA in rats, and its mechanism may involve regulating CRP levels, the ESR, and RFs via the TLR2/4-NF-κB signaling pathway.

Exploring the Mechanism of Zhibai Dihuang Decoction in the Treatment of Ureaplasma Urealyticum-Induced Orchitis Based on Integrated Pharmacology.

Background: Ureaplasma urealyticum (UU) infection is the most common cause of male infertility. Zhibai Dihuang Decoction (ZBDHD) can improve the rate of forwarding motility sperm, sperm deformity rate, seminal plasma zinc and refined berry sugar levels. Methods: The potential targets of ZBDHD are obtained from The Encyclopedia of Traditional Chinese Medicine (ETCM). Orchitis-related targets were collected from the Genecards and OMIM databases. The Cytoscape and the Database for Annotation, Visualization and Integrated Discovery (DAVID) were utilized to construct and analyzed the networks. Finally, a rat model of orchitis caused by UU infection was used to detect related indicators of mitochondrial energy metabolism using TUNEL apoptosis detection technology, loss cytometry, Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and Western Blot. Results: A total of 795 ZBDHD targets and 242 orchitis-related targets were obtained. The "ZBDHD- orchitis PPI network" was constructed and analyzed. ZBDHD can regulate signaling pathways and biological processes related to mitochondrial energy metabolism. The results of experimental studies have shown that ZBDHD maintains the integrity of sperm mitochondrial respiratory chain function by enhancing mitochondrial Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities, promotes the synthesis of mitochondrial ATP, and improves sperm energy supply, thereby improving the motility, vitality and survival rate of sperm, and effectively improving the quality of semen in UU-infected rats (p < 0.05). Conclusion:This study discovered the multi-pathway mechanism of ZBDHD intervention in UU-induced orchitis through integrated pharmacological strategies, which provides a reference for further research on the mechanism of ZBDHD intervention in orchitis in the direction of mitochondrial energy metabolism.

Pathological Relationship between Intestinal Flora and Osteoarthritis and Intervention Mechanism of Chinese Medicine.

Chinese medicine (CM) has a good clinical effect on osteoarthritis (OA), but the mechanism is not very clear. Evidence-based medicine researches have shown that intestinal flora plays a role in the pathogenesis and succession of OA. Intestinal flora affects the efficacy of CM, and CM can affect the balance of intestinal flora. This paper focuses on the relationship between intestinal flora, intestinal microenvironment, brain-gut axis, metabolic immunity and OA, and preliminarily expound the significance of intestinal flora in the pathogenesis of OA and the mechanism of CM intervention. The above discussion will be of great significance in the prevention and treatment of OA by CM from the perspective of intestinal flora.

[Effect of Chinese Herbal Extract HNA-1 on the Thymic Output Function in Simian Immunodeficiency Virus Chronically Infected Chinese Rhesus Macaques].

OBJECTIVE: To observe the effect of Chinese herbal extract HuNan A-1 (HNA-1) on the thymic output function in Simian immunodeficiency virus (SIV) chronically infected rhesus macaques. METHODS: Eight Chinese rhesus macaques had been infected by SIVmac239 for 16 to 21 months, and then they were randomly divided into the treatment group and the control group, 4 in each group. Monkeys in the treatment group were administered with HNA-1 by gastrogavage, once daily for 2 successive months, while those in the control group were administered with equal volume of normal saline by gastrogavage, once daily for 2 successive months. The general condition and body weight of monkeys were observed. Plasma viral loads were detected using real-time fluorescent quantitative PCR assay. CD4 percentages and counts, as well as naive CD subsets were detected using flow cytometry. T-cell receptor excision circles (TREC) were detected using real-time fluorescent quantitative PCR assay. The thymus tissue was pathologically observed using routine HE staining. The correlation between lesions of the thymus tissue, CD4 counts, naive CD counts, and TREC were analyzed. RESULTS: There was no statistical difference in body weight, viral loads, absolute CD ratios between the two groups after treatment (P > 0.05). The altered TREC multiple showed an obvious decreasing tendency in the control group, while it showed an increasing tendency in the treatment group (P < 0.05). In both groups, destroyed structures of the thymus tissue could be seen, filled with pink unstructured material. Increased connective tissues, lowered connective cell density, and confused arrangement could also be seen in the two groups, with no obvious difference. TREC contents were positively correlated with naive CD4 counts after removing extremum (r = 0.926, P = 0.001). Naive CD4 counts were positively correlated with CD4 counts (r = 0.961, P = 0.005). CONCLUSIONS: TREC content determination, as a marker of newly thymic emigrants, could be taken as a testing method for evaluating the thymic output function. Besides, HNA-1 treatment increased the thymic output significantly in SIV chronically infected monkeys. Correlation existed among TREC contents, naive CD4 counts, and pathologies of thymus tissues, especially in late infection stage.

[Effects of Maxing Shigan Decoction Decocted by Different Methods and Its Drug Containing Serum on Neuraminidase Activity of Influenza A Virus].

Objective To observe the effects of Maxing Shigan Decoction (MSD) decocted by different methods and its drug containing serum on neuraminidase ( NA ) activity of influenza A virus (IAV). Methods The effects of MSD decocted by different methods, its corresponding drug containing serums , and drug containing serum in inhibiting the proliferation of virus on NA activity of IAV were detected using 2-(4-methyl umbelliferyl )-α-D-N-acetyl neuraminic acid (MUNANA) as substrate. Results (1) Effect of MSD on NA activity of IAV: OD value was less in groups with Ephedra decocted 25-min earlier and 30-min earlier than the group with four drugs decocted at the same time (P <0. 05, P <0. 01) ; (2) Effect of MSD on NA activity of IAV: OD value was less in groups with Ephedra decocted 30-min earlier and 40-min earlier than the group with four drugs decocted at the same time (P <0. 05, P <0. 01) ; (3) In the process of inhibiting viral multiplication, effect of MSD containing serum on NA activity of IAV: OD value was less in groups with Ephedra decocted 5 -20 min earlier, 30 min earlier, 35 min earlier than the group with four drugs decocted at the same time (P <0. 05, P <0. 01). In terms of drug concentration, OA value decreased more in 6. 25% and 12. 50% MSD containing serums than in 25. 00% MSD containing serum (P <0. 01). Conclusion MSD decocted by different methods might lead to different anti-IAV effects.

[Effects of zhibal dihuang decoction on the pathological changes and the ultrastructure of the testicular tissue in the ureaplasma urealyticum-infected rats].

OBJECTIVE: To study the effects of Zhibai Dihuang Decocion (ZDD) on the pathological changes and the ultrastructure of the testicular tissue in the ureaplasma urealyticum (UU)-infected rats. METHODS: The UU infected animal models were established by the bladder inoculation. The 45 UU infected SD rats were randomly divided into four groups, i.e., the ZDD treatment group (at the daily dose of 2 g/100 g), the Minocycline group (at the daily dose of 10 mg/100 g), the model group, 15 in each group. Besides, another 15 rats were recruited as the sham-operation group. The medication was started 10 days after vaccination. Equal volume of normal saline was given to rats in the model group and the sham-operation group by gastrogavage for 22 successive days. Rats were sacrificed on the 2nd day of medication discontinuation. The testicle mass index was detected. The ultra-structure and the pathological changes of the testicular tissue were observed by optical microscope and transmission electron microscope. RESULTS: There was no significant difference in the rat testicular mass index (P>0.05). UU infection can lead to the pathological changes such as atrophy of seminiferous tubules, germ cell loss, and reduction of sperm cells in lumen, and to the ultrastructural changes such as spermatogenic cell nuclear membrane shrinkage, nuclear breakdown, and obvious edema of mitochondria. The pathological changes and the ultrastructures were improved in the medication groups. Rm and Rs the were not overlapping, and the difference was statistically significant (P<0.05). Rm, Rzh, and Rx were not overlapping, and the difference was statistically significant (P<0.05). Rzh and Rx were overlapping in 95% Cl with no statistical difference (P>0.05). CONCLUSIONS: UU infection can cause the pathological changes and the ultrastructural changes of the testicular tissue at the organic level and the cellular level. ZDD played therapeutic effects through ameliorating its pathological changes and the ultrastructural changes of spermatogenic cells.

[Effects of zhibal dihuang decotion on UU-infected rat's spermatogenic cell apoptosis and expressions of caspase-3 and caspase-9].

OBJECTIVE: To observe the effects of Zhibai Dihuang Decotion (ZDD) on the ureaplasma urealyticum (UU)-infected rats' spermatogenic cell apoptosis and expressions of Caspase-3 and Caspase-9. METHODS: 45 out of 60 male SD rats were randomly selected and made into the UU infected animal model. The rest 15 were taken as the sham-operation group. The UU infected model animals were then randomly divided into the model group, the minocycline group, and the ZDD group. From the 10th day after inoculation, normal saline was given to rats of the model group and the sham-operation group by gastrogavage, while corresponding medicines were given to rats in the minocycline group and the ZDD group. All rats were killed after 21 successive days of gastrogavage. The apoptosis rate of reproductive cells, Caspase-3 and Caspase-9 expression levels and ultrastructure changes of spermatogenic cells of each group were detected and compared. RESULTS: There was statistical difference in the positive rate of the UU cultivation results, the apoptosis rate of reproductive cells, Caspase-3 and Caspase-9 expression levels in the sham-operation group, the minocycline group, and the ZDD group when compared with the model group (P<0.05). There was statistical difference in the aforesaid indices in the minocycline group and the ZDD group when compared with the sham-operation group (P<0.05). Still there was no statistical difference in the aforesaid indices between the minocycline group and the ZDD group (P>0.05). CONCLUSIONS: UU infection can lead to the increasing of spermatogenic cell's apoptosis in rats. ZDD could actively inhibit the growth and production of UU with anti-UU. One of the mechanisms of ZDD in treating UU infection and improving the sperm quality is through regulating the expressions of the apoptosis effect factors Caspase-3 and Caspase-9.

[Efficacy of Maxing Shigan Decoction combined with Western medicine for pneumonia in children: a systematic review and meta-analysis].

OBJECTIVE: To systematically evaluate the clinical effects of Maxing Shigan Decoction (MXSGD), a compound traditional Chinese herbal medicine, combined with Western medicine on pneumonia in children. METHODS: In this study, the relative trials published from 1994 to 2008 were searched in Chongqing Weipu Database, Chinese Journal Full-text Database, Wanfang database, Chinese Biomedical Literature Database and other electronic database by using the method of Cochrane systematic review. At the same time the information from related journals, professional data and network were hand-searched. The methodological quality of the included trials was assessed by two evaluators, and homogeneous evaluation by meta-analysis was performed. Statistical analysis of clinical data was performed by using RevMan 4.2.7 software provided by the Cochrane Collaboration. RESULTS: A total of 146 reports were found, while only eight randomized controlled trials met the inclusion criteria. The methodology quality of the reports included in the study was evaluated by the Jadad scale, and the specific random method, allocation concealment, blinding and intention-to-treat analysis were not described in all of the eight trial reports. As MXSGD combined with Western medicine group (treatment group) was compared with Western medicine group (control group), the meta-analysis indicated that the odds ratio for the total effective rate was 4.06, and the 95% confidence interval was from 2.63 to 6.27. MXSGD combined with Western medicine was good at increasing the total effective rate as compared with Western medicine, and the difference was statistically significant (P<0.000 01). CONCLUSION: MXSGD combined with Western medicine can improve clinical symptoms and increase the total effective rate of the patients with pneumonia in children. However, its clinical effects should be further identified by high quality, multicenter and randomized controlled trials with large-scale design.

[Observation of the therapeutic effect of qianlie sanyu capsule on benign prostatic hyperplasia].

OBJECTIVE: To observe the clinical efficacy of Qianlie Sanyu Capsule on benign prostatic hyperplasia (BPH). METHODS: Seventy-two patients with BPH were randomly divided into a treatment group (40 patients) and a control group (32 patients), the former treated by Qianlie Sanyu Capsule and the latter by Longbishu. Observation were made on the changes of the patients' urination' symptoms, living quality, prostatic volume, Qmax uroflowmetry and excel urine before and after treatment. RESULTS: The total efficacy rates were 92.5% in the treatment group, and 72.5% in the control group. Comparison between the two groups showed significant difference (P < 0.01). The urination symptoms, living quality, Qmax uroflowmetry and the excel urine were better improved in the Qianlie Sanyu group than in the Longbishu. There were significant differences between the two groups (P < 0.05), but none in reducing effect on the prostatic volume. CONCLUSION: Qianlie Sanyu Capsule is an effective drug for BPH.