Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout.

ETHNOPHARMACOLOGICAL RELEVANCE: Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated. AIM OF THE STUDY: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action. MATERIALS AND METHODS: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions. RESULTS: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD. CONCLUSION: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4+ T cells via PI3K-AKT-mTOR pathway.

Stepwise changes in flavonoids in spores/pollen contributed to terrestrial adaptation of plants.

Protecting haploid pollen and spores against UV-B light and high temperature, 2 major stresses inherent to the terrestrial environment, is critical for plant reproduction and dispersal. Here, we show flavonoids play an indispensable role in this process. First, we identified the flavanone naringenin, which serves to defend against UV-B damage, in the sporopollenin wall of all vascular plants tested. Second, we found that flavonols are present in the spore/pollen protoplasm of all euphyllophyte plants tested and that these flavonols scavenge reactive oxygen species to protect against environmental stresses, particularly heat. Genetic and biochemical analyses showed that these flavonoids are sequentially synthesized in both the tapetum and microspores during pollen ontogeny in Arabidopsis (Arabidopsis thaliana). We show that stepwise increases in the complexity of flavonoids in spores/pollen during plant evolution mirror their progressive adaptation to terrestrial environments. The close relationship between flavonoid complexity and phylogeny and its strong association with pollen survival phenotypes suggest that flavonoids played a central role in the progression of plants from aquatic environments into progressively dry land habitats.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Tong Xie Yao Fang: A Classic Chinese Medicine Prescription with Potential for the Treatment of Ulcerative Colitis.

The prescription of Tong Xie Yao Fang (TXYF) was derived from the Yuan dynasty "Dan Brook Heart Law," which was a representative formula for treating liver-spleen disharmony, diarrhea, and abdominal pain. The prescription is composed of four herbs for soothing the liver and strengthening the spleen. TXYF is reportedly capable of eliminating discomfort in ulcerative colitis (UC). This classic formula has been widely used for regulating gastrointestinal motor dysfunction and repairing colon mucosa. This review aims to provide current information on the pharmacology and clinical research of TXYF in the treatment of UC, and to critically appraise that information, in order to guide the future clinical use and experimental study of TXYF in the treatment of UC. We searched online databases including PubMed, CNKI, and Google Scholar for research published between 2010 and 2020 on TXYF and its efficacy in the treatment of UC. The findings indicated that TXYF has anti-inflammatory and immunomodulatory effects, regulates cell signal transduction, brain-gut axis, and intestinal flora in UC, and may promote targeting of bone mesenchymal stem cells (BMSCs) to the colonic mucosa and accelerate healing of the colonic mucosal barrier. In addition, the results of clinical studies showed that TXYF has good efficacy and few adverse reactions in the treatment of UC. Although it has achieved some success, the research is limited by deficiencies; there is a lack of unified standards for the construction of UC animal models and for administration regimen. In addition, the dosage of TXYF is not consistent and lacks pharmacological verification, and clinical trial data are not detailed or sufficiently rigorous. Therefore, a more rigorous, comprehensive, and in-depth study of TXYF in the treatment of UC is needed.

[Effect of acupoint catgut embedding on intestinal mucosal epithelial barrier in ulcerative colitis rats].

OBJECTIVE: To observe the effect of acupoint catgut embedding on intestinal mucosal epithelial injury, and expression of epithelial tight junction proteins and mRNAs and protein kinase C(PKC) protein (intestinal mucosal epithelial barrier-related molecules) in rats with experimental ulcerative colitis (UC) of "deficiency-stasis" type, so as to explore its mechanisms underlying improvement of UC. METHODS: Male SD rats were randomly divided into normal control, UC model, medication (sulfasalazine, SASP) and catgut-embedding groups. The "deficiency-stasis" type UC model was established by gavage of adenine (10 mL/kg) for 2 weeks, cold Folium Sennae (10 mL/kg) for 2 weeks, and then enema of mixture solution of 5% trinitro-benzene-sulfonic acid (100 mg/kg) + 50% ethyl alcohol. Rats of the medication group received gavage of SASP. The catgut-embedment was applied to bilateral "Tianshu"(ST23),"Zusanli"(ST36), "Geshu"(BL17), "Pishu"(BL20), "Shenshu"(BL23) and "Dachangshu"(BL25), once every two weeks, 3 times altogether. The body mass was recorded, and histopathological changes of the colon tissues were observed after H.E. staining. The contents of serum D-lactic acid (D-LA), diamine oxidase (DAO) and protein kinase C (PKC) were detected by ELISA. The expression levels of occludin, claudin-8, cingulin and zonulin mRNAs and proteins and PKC protein of the colon tissues were detected by using quantitative real-time PCR and Western blot, separately. RESULTS: Compared with the control group, the body mass and expression levels of colonic occludin, claudin-8 and cingulin mRNAs and proteins were significantly lower (P<0.01), and the colonic mucosa damage index (CMDI) score, contents of serum D-LA, DAO and PKC, as well as the expression levels of zonulin mRNA and protein and PKC protein were significantly higher in the model group (P<0.01). In comparison with the model group, the body mass, and the expression levels of occludin, claudin-8 and cingulin mRNAs and proteins were significantly higher (P<0.05, P<0.01), whereas the CMDI score, expression levels of zonulin mRNA and protein and PKC protein were remarkably lower in both the medication group and acupoint embedding groups (P<0.05,P<0.01). No significant differences were found between the acupoint embedding and medication groups in all the indexes mentioned above (P>0.05). H.E. staining showed markedly swollen, disordered arrangement of intestinal mucosal cells, and hemorrhage with infiltration of inflammatory cells in the colonic tissues after modeling, which was relatively milder in both medication and acupoint embedding groups. CONCLUSION: Acupoint catgut embedding can reduce colonic tissue injury in UC rats, which may be related to its functions in regulating the expression of intestinal epithelial tight junction proteins and mRNAs and in inhibiting the activation of PKC protein.

Phenylpropanoid Derivatives Are Essential Components of Sporopollenin in Vascular Plants.

The outer wall of pollen and spores, namely the exine, is composed of sporopollenin, which is highly resistant to chemical reagents and enzymes. In this study, we demonstrated that phenylpropanoid pathway derivatives are essential components of sporopollenin in seed plants. Spectral analyses showed that the autofluorescence of Lilium and Arabidopsis sporopollenin is similar to that of lignin. Thioacidolysis and NMR analyses of pollen from Lilium and Cryptomeria further revealed that the sporopollenin of seed plants contains phenylpropanoid derivatives, including p-hydroxybenzoate (p-BA), p-coumarate (p-CA), ferulate (FA), and lignin guaiacyl (G) units. The phenylpropanoid pathway is expressed in the tapetum in Arabidopsis, consistent with the fact that the sporopollenin precursor originates from the tapetum. Further germination and comet assays showed that this pathway plays an important role in protection of pollen against UV radiation. In the pteridophyte plant species Ophioglossum vulgatum and Lycopodium clavata, phenylpropanoid derivatives including p-BA and p-CA were also detected, but G units were not. Taken together, our results indicate that phenylpropanoid derivatives are essential for sporopollenin synthesis in vascular plants. In addition, sporopollenin autofluorescence spectra of bryophytes, such as Physcomitrella and Haplocladium, exhibit distinct characteristics compared with those of vascular plants, indicating the diversity of sporopollenin among land plants.

Biodegradation of Polyethylene and Polystyrene by Greater Wax Moth Larvae (Galleria mellonella L.) and the Effect of Co-diet Supplementation on the Core Gut Microbiome.

Plastics waste and microplastics including polyethylene (PE) and polystyrene (PS) have been an environmental concern for years. Recent research has revealed that larvae of Galleria mellonella are capable of biodegrading low density PE film. In this study, we tested the feasibility of enhancing larval survival and the effect of supplementing the co-diet on plastic degradation by feeding the larvae beeswax or wheat bran as a co-diet. Significant mass loss of plastic was observed over a 21-day period, i.e., with respective consumption of 0.88 and 1.95 g by 150 larvae fed only either PS or PE. The formation of C═O and C-O containing functional groups and long chain fatty acids as the metabolic intermediates of plastics in the residual polymers indicated depolymerization and biodegradation. Supplementing beeswax and bran increased the survival rates but decreased the consumption of plastic. The changes in the gut microbiome revealed that Bacillus and Serratia were significantly associated with the PS and PE diets. Beeswax and bran showed different shaping effects on the core gut microbiome of larvae fed the PE and PS. These results suggest that supplementing the co-diet affected the physiological properties of the larvae and plastic biodegradation and shaped the core gut microbiome.

Qu-Zhuo-Tong-Bi Decoction Alleviates Gouty Arthritis by Regulating Butyrate-Producing Bacteria in Mice.

Qu-zhuo-tong-bi decoction (QZTBD) is a traditional Chinese medicine prescription used to treat hyperuricemia and gout with no obvious adverse effects. However, the mechanism by which QZTBD treats gout has not been fully explored. Here, we investigated the effects of QZTBD on gouty arthritis and its therapeutic mechanism from the perspective of the gut microbiome. Our results demonstrated that QZTBD was effective for reducing serum uric acid level and attenuating paw edema and mechanical allodynia. QZTBD promoted the abundance of butyrate-producing bacteria and the production of SCFAs. Further study revealed that QZTBD restored the intestinal barrier function, modulated the expression of GPR43 and ABCG2, suppressed the activity of key glycolysis-related enzymes, and inhibited the generation of intestinal inflammatory factors. These findings suggested that QZTBD is an effective therapeutic drug for gouty arthritis. Butyrate-producing bacteria and its metabolites SCFAs might act as a potential target of QZTBD.

Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis.

Tripterygium wilfordii Hook F (TwHF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tripterygium wilfordii Tablets (TWT) are the representative TwHF-based agents enrolled into the 2019 edition of Medicine Catalog for National Basic Medical Insurance, Injury Insurance, and Maternity Insurance. However, individual differences in TGT/TWT response across patients usually exist in the process of treating RA, implying that the clinical application of the two agents may not be standardized leading to the ineffective treatment and the risk of side effects. Growing evidence show that the bioactive constituents of TwHF may often have toxicity, the package insert of TGT and TWT may not be described in detail, and the therapeutic windows of the two agents are narrow. Thus, it is an urgent task to develop a standardized clinical practice guideline for TGT and TWT in the treatment of RA. In the current study, a group of clinical experts of traditional Chinese medicine and Western medicine in the research field of rheumatism diseases, pharmacists, and methodologists of evidence-based medicine were invited to select the clinical questions, to determine the levels of the evidence and the strength of the recommendations, and to develop the recommendations and good practice points. The guideline is formed based on the combination of clinical research evidence and expert experience (evidence-based, consensus, supplemented by experience). The clinical problems which are supported by clinical evidence may form recommendations, and the clinical problems without clinical evidence may form experts' suggestions. Both recommendations and experts' suggestions in this guideline summarized the clinical indications, usage, dosage, combined medication, and safety of TGT and TWT against RA systematically and comprehensively, which may offer a professional guidance in the context of the clinical application of the two TwHF-based agents.

Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC. MATERIALS AND METHODS: Primary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50µM CORT for 24h to induce gap junction damage. Rg1 (0.1, 1, or 10µM) or fluoxetine (1µM) was added 1h prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions. RESULTS: Treatment of primary astrocytes with CORT for 24h inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1µM and 10µM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation. CONCLUSION: These findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression.

[Effects of different concentrations of gubishu containing serum on the proliferation of rabbit articular chondrocytes in vitro culture].

OBJECTIVE: To investigate the effects of different concentrations of Gubishu containing serum on the proliferation of rabbit articular chondrocytes cultured in vitro. METHODS: Articular chondrocytes were obtained from the cartilage of 1-month rabbit and cultured in vitro. They were randomly divided into 8 groups,blank and Gubishu groups in different concentrations (5%, 10%,15%, 20%), MTT assay method was adopted to observe the influence of Gubishu containing serum with different concentrations to the proliferation of chondrocytes after incubated 1, 3, 5, 7 and 9 days. RESULTS: The proliferation of chondrocytes was dependent on the concentration in Gubishu groups. At same time point,there was significant value between every groups, 20% concentration was greatest (P<0.05); There was significant differences between 5%, 10% and 20% concentration of the blank groups at same time point (P<0.05), and was not between 15% and 20% concentration at the 1, 3, 5 and 7 days (P>0.05), 20% concentration of the blank group was greatest. 20% concentrations of Gubishu containing serum was significantly greater than 20% concentrations of blank group at the 1, 3, 5 and 7 days (P<0.05). CONCLUSION: 20% concentrations of Gubishu containing serum can significantly increase the proliferation of chondrocytes, and bring the logarithmic growth period forward to the 3 day.

[Postmenopausal osteoporosis of liver and kidney deficiency type treated with acupoint catgut embedding by stages].

OBJECTIVE: To explore the better treatment of postmenopausal osteoporosis of liver and kidney deficiency type. METHODS: One hundred and five cases were randomly divided into an observation group, a control group A and a control group B equally. In control group A, Calcichew D3 tablets were taken with oral administration; in control group B, Calcichew D3 tablets and Xianling Gubao capsule were taken with oral administration. In observation group, Calcichew D3 tablets and acupoint catgut embedding were applied; Shenshu (BL 23), Ganshu (BL 18), Jiaji (EX-B 2) and Weizhong (BL 40) etc. were selected at acute stage; Shenshu (BL 23) and Ganshu (BL 18) etc. were selected at remission stage, once every half a month and 6 months treatment in all. The Visual Analogue Scale (VAS), bone mineral density(BMD), estradiol (E2) and clinical effects were compared among groups. RESULTS: After 3 and 6 months treatment, the scores of VAS were reduced among groups (all P < 0.01); the reduction in observation group and control group B was superior to that in control group A (all P < 0.001), and it was more obvious in observation group than that in control group B (both P < 0.001). After 6 months treatment, lumbar BMD and the serum level of Ez improved obviously in observation group and control group B (all P < 0.01). The comparison among groups after treatment showed that the BMD in observation group and control group B was superior o o that in control group A (P < 0.01, P < 0.05); the serum level of E2 in observation group was superior to that in control group B and control group A (both P < 0.001), and it in control group B was superior to that in control group A. The total effective rate was 91.4% (32/35) in observation group, superior to that in control group A (57.1%, 20/35); and the total effective rate was 82. 9% (29/35) in control group B, superior to that in control group A. CONCLUSION: Calcichew D3 tablets and acupoint catgut embedding therapy can relieve the pain caused by postmenopausal osteoporosis of liver and kidney deficiency, improve the bone mineral density and serum level of estradiol; in brief, it is the better method.

[Controlled clinical trials on the treatment and prevention of shoulder and back fasciitis using horizontal bar exercises].

OBJECTIVE: To explore an exercise method for the prevention and treatment of the patients with shoulder and back fasciitis. METHODS: From 2006.8 to 2008.3, 120 patients with shoulder and back fasciitis were randomly divided into control group (n = 60, including 21 females and 39 males, the average age was (47.0 +/- 12.0) years, and the average course of disease was (14.1 +/- 12.0) months) and treatment group (n = 60,including 19 females and 41 males, the average age was (43.7 +/- 9.9) years, and the average course of disease was (16.4 +/- 13.4) months). The patients in the control group received massage therapy and the ones in the treatment group were treated with massage therapy and horizontal bar exercise. After 3 weeks treatment, the curative effects of the patients in two groups were observed. All the patients were followed up for 6 to 26 months, the recurrence were observed. RESULTS: After 3 weeks treatment, the scores of pain, sense of heaviness, strip sign, tenderness, shoulder and back function of the patients in two groups had significant differences compared with those before treatment (all P < 0.01). After treatment, the scores of pain, sense of heaviness, strip sign, tenderness, shoulder and back function of the patients in the treatment group were lower than those in the control group (P < 0.05). After 6 to 26 months following-up, the rate of recurrence in the treatment group was lower than that in the control group (P < 0.01). CONCLUSION: Horizontal bar exercise is a simple, no expense and effective method in the prevention and treatment of shoulder and back fasciitis, which can improve the effect of the treatment and reduce the rate of recurrence.

[The application of infrared spectra and clustering analysis in the discrimination of geographical origin of Flos Chrysanthemi].

OBJECTIVE: To identify the origin of Flos Chrysanthemi. METHODS: FTIR (Fourier transform infrared spectroscopy) and SIMCA (sofe independent modeling of class analogy). RESULTS: The correctness of every classification was higher than 60%. CONCLUSION: This approach was proved to be a reliable and practicable method for the discrimination of geographical origin of Chrysanthemum.