Kidney Yang Research Articles

Exploring the mechanism of action of Qian Lie Xing Fang during the treatment of benign prostatic hyperplasia via network pharmacology and molecular dynamics simulation analyses.

This study aimed to explore the historical research progress on benign prostatic hyperplasia from the perspective of traditional Chinese medicine theory and the treatment of benign prostatic hyperplasia (BPH) with Qian Lie Xing Fang (QLXF) via the warming and tonifying of kidney yang, promotion of blood circulation, and clearing of meridians. First, network pharmacology analysis was used to screen and identify possible pathways for BPH treatment with QLXF. Subsequently, molecular docking analysis helped explore the mechanism of action by which the components of QLXF affected androgen receptor (AR) and type 5 phosphodiesterase inhibitor (PDE-5) levels. Targets for treatment with QLXF were identified from the online Mendelian inheritance in man and DisGeNET databases. BPH-related genes were identified using GeneCards and online Mendelian inheritance in man databases, and their intersection was used to construct a protein-protein interaction network analysis graph. Subsequently, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed. The semiflexible docking of the ingredients of QLXF acting on the 2 targets was performed via molecular docking and molecular dynamics simulation, to elucidate the mechanism of action by which the active ingredients affect AR and PDE-5 levels further. This enabled us to explore the pattern of interactions between small active ingredient molecules, the target protein, and the stability after binding at the microscopic level. Gene ontology enrichment analysis showed that QLXF affected several processes, such as DNA transcription factor binding, kinase binding, protein homodimerization activity, protein structure domain-specific binding, and protein-coupled amine receptor activity in BPH patients. KEGG results showed that chemical carcinogenic reactive oxidative species and the JAK-STAT, Pl3k-Akt, FoxO, NF-κB, and other pathways were significantly enriched. Conducting molecular docking studies to investigate the interaction of active components from QLXF with AR and PDE-5, it was found that MOL002260 may possess the potential to inhibit PDE-5 activity, while MOL010578 may exhibit the capability to inhibit AR activity. QLXF is closely associated with various biological processes and KEGG signaling pathways related to BPH. The active ingredients of QLXF were investigated for their interactions with AR and PDE-5, with a primary focus on the small molecules MOL002260 and MOL010578.

Transcriptomic analysis the mechanisms of anti-osteoporosis of desert-living Cistanche herb in ovariectomized rats of postmenopausal osteoporosis.

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis.

An integrated fecal metabolomic based on 1 H-NMR and UPLC-QTOF-MS revealed the preventive mechanism of Gushudan on glucocorticoid-induced osteoporotic rats.

Gushudan (GSD) has the effect of strengthening bones and nourishing kidneys. However, its specific intervention mechanism still remains unclear. In this study, to investigate the pathogenesis of glucocorticoid-induced osteoporosis (GIOP) and the preventive mechanism of GSD on GIOP, fecal metabolomics based on 1 H-NMR and ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry method was established. The changes in endogenous metabolites and the relevant metabolic pathways in the control group, model group, and GSD treatment group were investigated via multivariate statistical analysis. As a result, a total of 39 differential metabolites were identified. Of these, 22 metabolites, such as L-methionine, guanine, and sphingosine, were newly discovered as differential metabolites of GIOP. Amino acid metabolism, energy metabolism, intestinal flora metabolism, and lipid metabolism were significantly changed in the fecal profiles of GIOP rats, and GSD could play an anti-osteoporosis role by regulating these metabolic pathways. Finally, compared with our previous study of the GSD to prevent kidney yang deficiency syndrome, this study suggested that there were some identical differential metabolites and metabolic pathways. It showed that there was some correlation among the metabolic profiles of the intestine, kidney, and bone in GIOP rats. Therefore, this study offered new insights into the in-depth understanding of the pathogenesis of GIOP and the intervention mechanism of GSD.

Effectiveness of chromic catgut implantation in men with idiopathic infertility

Introduction: the treatment of idiopathic male infertility is empirical and controversial.Objective: to assess the effectiveness of chromic catgut implantation at selected acupuncture points according to traditional Chinese syndromic diagnosis in men with idiopathic infertility.Methods: quasi-experimental study with pre-test-post-test and control group, in 135 patients with idiopathic infertility divided into: study group (67 treated with catgut implantation) and control group (68 treated with medication). A traditional medical history was taken and descriptive and inferential statistics were used.Results: mean age was similar in both groups (33,90 ± 6,28 years study group and 33,68 ± 5,6 years control group). Patients with Kidney yang vacuum predominated (55,2 % study group and 52,9 % control group). Both groups showed highly significant differences in sperm concentration, motility and morphology before and after treatments and between groups. Clinical improvement (64,2 % vs. 8,8 %), spermogram normalisation (53,7 % vs. 16,2 %) and pregnancy achievement (17,9 % vs. 4,4 %) were higher in patients treated with chromic catgut implantation compared to those using Clomiphene.Conclusions: chromic catgut implantation in selected acupuncture points according to traditional Chinese syndromic diagnosis in men with idiopathic infertility is effective because it improves sperm concentration, motility and morphology, normalises the spermogram and contributes to achieving pregnancies with increased fertility, to a greater extent than treatment with Clomiphene; together with the clinical improvement of the patients

Effects of long-snake moxibustion on the HPA axis and liver 11β-HSD1 expression in rats with kidney yang deficiency: 长蛇灸对肾阳虚大鼠HPA轴及肝脏11β-HSD1的影响

ObjectiveTo observe the effects of long-snake moxibustion on the hypothalamic-pituitary-adrenocortical (HPA) axis and hepatic 11β-hydroxy steroid dehydrogenase type 1 (11β-HSD1) expression in rats with kidney yang deficiency to provide a basis for later in-depth exploration of the action mechanism of long-snake moxibustion on such rats. MethodsFifteen SPF-grade, male, SD rats were randomly divided into a blank control group, a model group, and a long-snake moxibustion treatment group, with five rats in each group. Hydrocortisone powder (30 mg/kg) was administered by gavage at a volume of 10 mL/kg to prepare the rat model of kidney yang deficiency. After successful modeling, the rats in the long-snake moxibustion treatment group underwent long-snake moxibustion treatment every other day (along the governor vessel from Dazhui (GV14) to Shenshu(BL23), for a period of 14 days. The remaining two groups were secured in the same way as the long-snake moxibustion treatment group, although they did not receive any treatment. The body weight, rectal temperature, and spontaneous activity count of the rats, as well as serum levels of corticotropin releasing hormone (CRH) and corticosterone (CORT) were detected by ELISA before modeling, after modeling, and after treatment. The amount of 11β-HSD1 protein in rat liver was determined by immunohistochemistry and Western blot analysis. ResultsCompared with the rats in the blank control group, those in the model group exhibited a significant decrease in the trend of body weight growth and in rectal temperature (P <0.05), as well as a slight yet non-significant decrease in spontaneous activity count (P >0.05); compared with the rats in the model group, the rats in the treatment group exhibited a significant increase in rectal temperature (P <0.05) and in spontaneous activity count (P <0.05). Moreover, after 14 days of treatment, compared with the rats in the blank, the rats in the model group exhibited a significant decrease in serum CORT content (P <0.05) and in the expression of 11β-HSD1 in the liver (P <0.05), as well as a slight yet non-significant decrease in serum CRH content (P >0.05); compared with the rats in the model group, the rats in the treatment group exhibited a significant increase in serum CRH content (P <0.05) and in the expression of 11β-HSD1 in the liver (P <0.05), as well as a slight yet non-significant increase in serum CORT content (P >0.05). ConclusionLong-snake moxibustion can increase the rectal temperature and spontaneous activity count of rats with kidney yang deficiency, improve the function of the HPA axis, and increase the expression of 11β-HSD1 in the liver.

Decipher the pharmacological mechanisms of raw and wine-processed Curculigo orchioides Gaertn. on bone destruction in rheumatoid arthritis rats using metabolomics.

Curculigo orchioides Gaertn. (CO), a traditional Chinese herb recorded in Chinese Pharmacopoeia, can nourish kidney yang, strengthen bones, and dispell cold-dampness. Raw CO (rCO) and wine-processed CO (pCO), the main processed products of CO for clinical application, show differences in nourishing kidney yang and ameliorate osteoporosis. However, the difference in efficacy and mechanism of rCO and pCO on bone destruction in rheumatoid arthritis (RA) remain unclear. To compare the pharmacodynamics of rCO and pCO in the treatment of bone destruction in RA and to reveal the potential mechanism by which rCO and pCO exert effects by metabolomics approach. Ultra-high performance liquid chromatography Q exactive mass spectrometry (UHPLC-Q-Exactive-MS) combined with multivariate data analysis was applied to identify the differential chemical components in rCO and pCO. Collagen-induced arthritis (CIA) rats were orally administrated with different doses of rCO and pCO for 4 weeks. The body weight, paw swelling, arthritis scores, serum inflammatory cytokines concentration, knee tumor necrosis factor (TNF)-α, interleukin (IL)-6 protein levels, and inflammatory cell infiltration were determined to investigate the effects of rCO and pCO on arthritic symptoms and inflammatory responses in CIA rats. The effects of rCO and pCO on bone destruction were assessed using safranin O-fast green and tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemical analysis of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) proteins, and micro-computed tomography (micro-CT) in rats. In addition, metabolomics was performed to explore the mechanism of rCO and pCO against bone destruction in RA. A total of 41 chemical constituents were identified in both rCO and pCO, 9 of which were screened out as discriminatory compounds. According to the pharmacodynamic assays, pCO exhibited a stronger effect than rCO in attenuating the severity of arthritis, reducing inflammation, and inhibiting bone destruction. The metabolomics results showed that pentose phosphate pathway was the key metabolic pathways regulated by rCO, while pCO regulated multiple metabolic pathways including phenylalanine metabolism pathways, phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and glycerophospholipid metabolism pathways. pCO displayed a better effect on alleviating bone destruction in RA was than rCO. This might be associated with that pCO can decrease inflammation in RA through regulating more metabolism pathways.

"Huoling Shengji granule" for amyotrophic lateral sclerosis: protocol for a multicenter, randomized, double-blind, riluzole parallel controlled clinical trial.

There is still a large demand for effective treatments to delay disease deterioration in amyotrophic lateral sclerosis (ALS). Typical symptoms of ALS are considered "flaccidity syndrome" in traditional Chinese medicine (TCM). Huoling Shengji Granule (HLSJ) is a TCM formula used to treat flaccidity syndrome. Results of preclinical tests and a previous clinical study support HLSJ as a novel drug for ALS patients. This trial proposed to examine whether a 48-week course of HLSJ is effective and safe for ALS patients diagnosed with the Chinese medicine syndrome of spleen qi insufficiency and kidney yang deficiency. In this phase II, multicenter, randomized, double-blind, riluzole parallel-controlled, superiority-design study, eligible participants had the equal opportunity to be assigned to receive either HLSJ or riluzole randomly. Eleven specialized ALS centers in Mainland China will recruit 144 patients for this trial. The primary and secondary outcomes included the change in the ALSFRS-R score and the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) from baseline to Week 48. Here, we endeavored to evaluate TCM for ALS using a standard evidence-based approach for the first time. In addition, the ROADS, a self-report linear-weighted questionnaire, was selected as a secondary outcome measure. We expect to offer a new reference for the outcome evaluation of ALS trials.Clinical trial registration:http://www.Chictr.org.cn, identifier ChiCTR2100044085.

Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway

Ethnopharmacological relevanceDipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. Aim of the studyThe purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR. Materials and methodsThe model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-α), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS. ResultsThe results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-α were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified. ConclusionThis study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed.

Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang.

Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear. Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an "active compounds-targets-metabolic pathways" network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed. Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil. Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.

16S rDNA sequencing combined with metabolomics profiling with multi-index scoring method reveals the mechanism of salt-processed Semen Cuscuta in Bushen Antai mixture on kidney yang deficiency syndrome

Kidney yang deficiency syndrome (KYDS) is a classic syndrome of traditional Chinese medicine (TCM). The salt-processed product of Semen Cuscuta (YP) is the monarch drug in Bushen Antai Mixture (BAM), can improve the reproductive dysfunction caused by KYDS, and the effect is better than that of raw products of Semen Cuscuta (SP). However, its mechanism is not completely clear yet. In this study, an integrated strategy combining untargeted metabolomics with microbiology was used to explore the mechanism of YP in the BAM improving KYDS. 16S rDNA gene sequencing showed that BAM containing YP (Y-BAM) had a significantly better regulatory effect on Desulfobacterota and Desulfovibrionaceae_unclassified than BAM containing SP (S-BAM). Untargeted metabolomics studies showed that Y-BAM significantly regulated 4 metabolites and 4 metabolic pathways. In addition, multi-index analysis showed that the effect of Y-BAM on arachidonic acid metabolism, tyrosine metabolism, purine metabolism, fructose and mannose metabolism and total metabolism was closer to that of the control group compared to S-BAM. The analysis of serum biochemical indexes showed that Y-BAM had more significant regulating effect on the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) and superoxide dismutase (SOD) in serum of KYDS rats compared to S-BAM. Spearman correlation analysis showed that there was a significant correlation between intestinal microorganisms and metabolites and serum biochemical indexes. For example, Desulfovibrionaceae_unclassified was positively correlated with arachidonic acid, and negatively correlated with SOD and LH. This study suggests that YP may enhance the regulation of intestinal flora and endogenous metabolism of KYDS, so that BAM shows a better therapeutic effect on KYDS, which also reasonably explains why BAM uses Semen Cuscuta stir-baked with salt solution.

Exploring the Combination Characteristics and Mechanism of Kidney Tonifying Effects of Kidney Qi Pill and Right Return Pill Based on the Theory of "Tonifying and Diarrhea"

Kidney Qi Pill is from Zhang Zhongjing's Jinkui Yaolve in the Han Dynasty, while Right Return Pill is from Zhang Jingyue's "JingYue QuanShu" in the Ming Dynasty, although the two sides were created in different dynasties, they are both kidney tonic formulas and are still used today. Drugs such as " three tonics " and "three diarrheas" and various drugs such as "less fire and more anger" in kidney qi pills can achieve tonify the kidney qi, while Right Return Pill is based on the Kidney-Qi Pill by deleting the "three tonics" and retaining the "three diarrhoeas". Both of them have the effect of warming the kidney yang, but Kidney Qi Pill aims to warm the kidney yang and transform the kidney qi, while Right Return Pill fills the kidney essence and helps the kidney yang. Its mechanism of action is the same and different, and at the same time, the "three tonics" are used to "seek yang in the yin", and the difference is the "three diarrhea" drugs and filling in the fine matching and trade-offs of the boutique. This paper aims to compare and analyze the characteristics of the combination of kidney qi pill and Right Return pill and modern molecular mechanism. In order to provide reference for the advantages of these two directions to study the drug and compatibility mechanism.

Chinese medicinal formulae treat inflammatory bowel diseases through maintaining gut flora homeostasis

Inflammatory bowel disease(IBD) is a chronic and recurrent inflammatory disorder of the gut, including Crohn's disease(CD) and ulcerative colitis(UC). The occurrence and development of IBD involves multiple pathogenic factors, and the dybiosis of gut flora is recognized as an important pathogenic mechanism of IBD. Therefore, restoring and maintaining the balance of gut flora including bacteria and fungi has become an effective option for IBD treatment. Based on the theoretical basis of the interaction between gut flora and IBD, this paper followed the principle of clinical syndrome differentiation for IBD therapy by traditional Chinese medicine(TCM), and summarized several Chinese medicinal formulae commonly used in IBD patients with large intestine damp-heat syndrome, intermingled heat and cold syndrome, spleen deficiency and dampness accumulation syndrome, spleen and kidney yang deficiency syndrome, liver stagnation and spleen deficiency syndrome, and severe heat poisoning syndrome. The therapeutic and regulatory effects of Shaoyao Decoction, Qingchang Suppository, Wumei Pills, Banxia Xiexin Decoction, Shenling Baizhu Powder, Lizhong Decoction, Sishen Pills, Tongxie Yaofang, Baitouweng Decoction, Gegen Qinlian Decoction, and Houttuyniae Herba prescriptions on gut flora of IBD patients were emphasized as well as the mechanisms. This study found that Chinese medicinal formulae increased the abundance of Bacteroidetes, Bifidobacteria, Lactobacillus, and other beneficial bacteria producing short-chain fatty acids, and reduced the abundance of Enterobacteriaceae and other harmful bacteria to restore the balance of gut flora, thus treating IBD. Confronting the recalcitrance and high recurrence of IBD, Chinese medicinal formulae provide new opportunities for IBD treatment through intervening dysbiosis of gut flora.

Influence of far‐infrared vacuum drying on drying kinetics and quality characteristics of Cistanche slices

AbstractIn order to improve the drying efficiency and quality of Cistanche, the effects of far‐infrared vacuum drying on drying rate, active component content and microstructure of Cistanche slices were studied with drying temperature, slice thickness and irradiation height as experimental indexes. The results showed that the drying process of Cistanche was mainly concentrated in the deceleration stage. When the drying temperature was 55°C, the slice thickness was 4 mm, the irradiation height was 150 mm, and the time to reach the safe water content (10% w.b.) of Cistanche was the shortest. With the increase in drying temperature, slice thickness and irradiation height, the contents of phenylethanoid glycosides, iridoids, polysaccharides, total phenols and total flavonoids in dried products increased first and then decreased. Compared with natural drying, the samples dried by far‐infrared vacuum have more pores and better structural integrity. Phenylethanol glycosides and iridoid compounds, such as echinacoside and verbascoside, in Cistanche have significant effects in anti‐inflammatory and analgesic, tonifying kidney yang, anti‐Alzheimer's disease and protecting various organs and systems of the body. In this study, the slices of Cistanche were processed by far infrared vacuum drying, and the effects of different drying conditions on drying rate, effective moisture diffusion coefficient, active ingredient content, antioxidant activity, color and microstructure of dried Cistanche were studied. The drying process was fitted by a drying model, in order to obtain dried Cistanche products with better quality, and provide theoretical basis and technical support for the actual production of Cistanche.Novelty impact statement Midilli model could better describe the variation law of water content in the drying process of Cistanche. Compared with natural drying, the surface samples dried by far‐infrared vacuum have no cracks and good boundary integrity. The optimal process parameters (55°C, 4 mm, 310 mm) for far‐infrared vacuum drying of Cistanche slices were determined by the entropy value method.

Study of Correlation between Intestinal Microbiota and Traditional Chinese Medicine Syndrome of Patients with Colon Cancer.

Objective This research aims to study the material basis of the formation and specific bacteria of traditional Chinese medicine (TCM) syndrome from the characteristics of the intestinal microbiota of patients with colon cancer (CC) before and after the operation. Methods A cross-sectional study was conducted on 84 patients with CC and 24 healthy controls. A total of 168 and 24 stool samples were collected from CC patients before and after the operation and healthy controls. DNA was extracted from 192 stool samples and then amplified using PCR. The V3-V4 high variable areas were analyzed by 16s rDNA sequencing. Results The community diversity, in descending order, was the healthy control group and postoperative and preoperative groups of CC patients. The abundance of beneficial bacteria was postoperative group of CC patients > healthy control group > preoperative group of CC patients. Among the comparisons of the intestinal microbiota of preoperative groups of CC patients with different TCM syndromes, the community diversity in descending order was damp heat accumulation (DHA), spleen deficiency and dampness (SDD), spleen and kidney yang deficiency (SKYD), liver and kidney yin deficiency (LKYD), and deficiency of qi and blood (QBD), respectively. Specific microbiome analysis showed that the differences in the abundance of 42 taxons were statistically significant among the preoperative groups of CC patients with the five TCM syndromes and the healthy control group. While comparing the intestinal microbiota of postoperative groups with the five TCM syndromes, the community diversity in descending order is DHA, SDD, LKYD, SKYD, and QBD. Specific microbiome analysis showed that the differences in the abundance of 46 taxons were statistically significant among the postoperative groups of CC patients with the five TCM syndromes and the healthy control group. Streptococcus and Streptococcus mutans showed no statistical significance between the preoperative group and postoperative groups of CC with DHA syndrome (P > 0.05). Bacteroides at phylum and genus levels showed that there was no statistical significance between the preoperative group and the postoperative group of CC with SKYD syndrome (P > 0.05). Conclusions Before and after surgery, with the deterioration of TCM syndrome: DHA ⟶ SDD ⟶ SKYD ⟶ LKYD ⟶ QBD, the number of beneficial bacteria in CC patients' intestines decreased while the number of pathogenic bacteria increased, and the community structure of intestinal microbiota tends to be unitized, indicating a serious intestinal microbiological disorder. After radical surgery and perioperative intervention, the intestinal microbiota diversity and community structure of postoperative CC patients were closer to those of healthy people than preoperative. However, they were still imbalanced. The intestinal microbiota of CC patients with different TCM syndromes differs significantly, which is important for understanding the pathogenesis of CC in TCM. The DHA and SKYD syndromes in CC patients before and after surgery showed significant differences in the microbial structure. Streptococcus and Streptococcus mutans were the specific species with a significant difference in CC patients with DHA syndrome, while bacteroides were the specific species in CC patients with SKYD syndrome.

Exploring and Verifying the Mechanism and Targets of Shenqi Pill in the Treatment of Nonalcoholic Steatohepatitis via Network Pharmacology and Experiments.

Shenqi pill (SQP), a famous traditional Chinese medicine (TCM) herbal formula derived from Jinguiyaolue (Synopsis of Prescriptions of the Golden Chamber), has long been used to treat kidney yang deficiency syndrome. According to the TCM treatment principle that the liver and kidney are homologies, the clinical use of SQP in the treatment of nonalcoholic steatohepatitis (NASH) has achieved a good effect. However, the active targeted genes and underlying mechanism remain unclear. In this study, we aimed to explore the treatment mechanism of SQP in NASH rats, which may further contribute to the in-depth exploration of SQP in clinical applications. Network pharmacology analysis was used to screen the target genes of SQP for NASH treatment based on public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) analysis were used to search for crucial target genes and mechanisms. UPLC–MS/MS was used to verify the active compounds of the SQP screened. The hepatic pathology and biochemical indicators of rats were used to judge the modeling results and the curative effect of SQP. Western blotting and qRT–PCR were used to verify the expression of crucial target genes at the protein and RNA levels, respectively. Network pharmacology analysis and bioinformatics analysis showed that PTGS2, JUN, MYC, and CDKN1A might be crucial target genes in the primary mechanism of SQP in treating NASH and improving the inflammatory response. The UPLC–MS/MS results confirmed that the hub active compound, quercetin, screened out through the TCMSP database, is indeed present in SQP. Hepatic injury and lipid metabolism indicators of NASH rats were significantly improved after SQP treatment. The results of WB and qRT–PCR showed that the expression of PTGS2, JUN, MYC, and CDKN1A was higher in NASH rats than in normal rats and decreased after SQP treatment. The expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) was reduced after SQP treatment, which confirmed that SQP could improve hepatic inflammation in rats. These results suggested that SQP could ameliorate NASH in rats, and that quercetin may be the critical active compound that exerts the therapeutic effect.

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis.

Background Gubitong Recipe (GBT) is a prescription based on the Traditional Chinese Medicine (TCM) theory of tonifying the kidney yang and strengthening the bone. A previous multicentral randomized clinical trial has shown that GBT can effectively relieve joint pain and improve quality of life with a high safety in treating osteoarthritis (OA). This study is aimed at elucidating the active compounds, potential targets, and mechanisms of GBT for treating OA. Method The network pharmacology method was used to predict the key active compounds, targets, and mechanisms of GBT in treating OA. An OA rat model was established with Hulth surgery, and the pathological changes of articular cartilage were observed to evaluate the effects of GBT. Chondrocytes were stimulated with LPS to establish in vitro models, and key targets and mechanisms predicted by network pharmacology were verified via qRT-PCR, ELISA, western blot, and immunofluorescence. The Contribution Index Model and molecular docking were used to determine the key active compounds of GBT and the major nodes affecting predicted pathways. Result A total of 500 compounds were acquired from related databases, where 87 active compounds and their 254 corresponding targets were identified. 2979 OA-related genes were collected from three databases, 150 of which were GBT-regulating OA genes. The compound-target network weight analysis and PPI results showed that IL-6 and PGE2 are key targets of GBT in treating OA. KEGG results showed that PI3K/AKT, Toll-like receptor, NFκB, TNF, and HIF-1 are the key signaling pathways. An in vivo experiment showed that GBT could effectively suppress cartilage degradation of OA rats. In vitro experiments demonstrated that GBT can inhibit the key targets of KEGG-related pathways. Molecular-docking results suggested that luteolin, licochalcone A, and β-carotene were key targets of GBT, and the mechanisms may be associated with the NFκB signaling pathway. Blockage experiments showed that the NFκB pathway is the key pathway of GBT in treating OA. Conclusion This study verified that GBT can effectively protect articular cartilage through multitarget and multipathway, and its inhibitory effect on the NFκB pathway is the most key mechanism in treating OA.

Norlignans and phenolics from genus Curculigo protect corticosterone-injured neuroblastoma cells SH-SY5Y by inhibiting endoplasmic reticulum stress-mitochondria pathway

Ethnopharmacological relevanceThe plants of genus Curculigo are divided into the Section Curculigo and the Section Capitulata, which are mainly distributed in southeastern and southwestern China. Various ancient chinese books record that these plants were used as an important herb for tonifying kidney yang. Traditional Chinese medicine often draws on this property to treat depression syndrome. Thus genus Curculigo has potential for the treatment of neurodegenerative diseases (ND). The study showed that phenolics were the main characteristic components of plants in the Section Curculigo, represented by orcinol glucoside and curculigoside; the norlignans, with Ph-C5-Ph as the basic backbone, were the main characteristic components of the Section Capitulata. However, there is a lack of sufficient scientific evidence as to whether these two types of ingredients have neuroprotective effects. Aim of the studyTo determine the neuroprotective effects of phenolics and norlignans in genus Curculigo on human neuroblastoma cells SH-SY5Y. To discuss their structure-activity relationship and screen for compounds with high activity and neuroprotective effects. To reveal that the amelioration of endoplasmic reticulum (ER) stress by two classes of compounds is mediated by the PERK/eIF2α/ATF4 pathway. Materials and methodsThe cytotoxicity of 17 compounds was assayed by MTT. SH-SY5Y cells were damaged by corticosterone (Cort) (200 μM) for 24 h and then co-administered with 17 compounds (0.1–100 μM) and Cort (200 μM) for 24 h. Cell survival was determined by MTT assay. Apoptosis rate, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels were detected using flow cytometry. Intracellular Ca2+ levels were detected using a fluorescent probe. Cellular mitochondrial and ER damage was observed using transmission electron microscopy (TEM). ER stress and apoptotic pathway-related proteins (BiP, CHOP, cleaved caspase-3, cleaved caspase-9, Bax/Bcl-2), and the expression level of PERK/eIF2α/ATF4 pathway was measured via western blot (WB). ResultsThe experimental data showed that Cort treatment of SH-SY5Y cells resulted in decreased cell survival and increased apoptosis, mitochondrial depolarization, ROS, and intracellular Ca2+ levels. The co-action of 17 compounds and Cort for a period of time significantly increased cell survival. Compounds 3, 7, 12, 13 also reduced apoptosis rate, mitochondrial depolarization, ROS and intracellular Ca2+ levels in the subsequent experiments. In addition, TEM observed that Cort caused mitochondrial and ER damage, and the damage was improved after treatment. WB analysis obtained that Cort increased the expression of apoptotic and ER stress-related proteins and activated pathway expression. However, in the presence of compounds 3, 7, 12, 13, the expression of BiP, CHOP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 was significantly reduced, and the phosphorylation of PERK and eIF2α and the expression of ATF4 were inhibited. ConclusionThis study found that one phenolic (3) and three norlignans (7, 12, 13) from genus Curculigo have significant neuroprotective effects. The results of the structure-activity relationship indicated that the glucosyl polymeric norlignans and the phenolics with benzoic acid as the parent nucleus were more active. The neuroprotective effect of three norlignans is the latest discovery. This finding has important research value in the field of prevention and treatment of neurodegenerative diseases.

Ovulatory disorders under "common therapeutic principle for different diseases": essence of "Tiangui" and relationship with ovulation disorders

The essence of the &quot;common therapeutic principle for different diseases&quot;(Yibing Tongzhi in Chinese for short) is the disease-syndrome combination, which is the classic mode of understanding and treating diseases in traditional Chinese medicine(TCM). This study holds the view that Yibing Tongzhi is the optimal treatment mode of ovulation disorders since ovulation disorders have the common pathogenesis, i.e., &quot;kidney-Tiangui(reproduction-stimulating essence)-Chongren(thoroughfare and conception vessels)-uterus axis&quot; disorder. Kidney is an important basis of the reproductive axis, where kidney essence, kidney yang, and kidney Qi are the key substances and driving forces promoting the operation of the reproductive axis. Chongren is an important transmission path. &quot;Tiangui&quot;, the upstream substance related to the heart, brain and kidney with a connecting effect, plays a key role in the ovulation mechanism and is a representative of the reproductive axis function. There are four common Tiangui abnormalities in ovulatory disorders, including hypomenorrhea, yin and yang deficiency, abnormal exuberance of extreme yin, and abnormal phase. The dynamic changes of &quot;Tiangui&quot; can induce different diseases, such as polycystic ovary syndrome and hyperprolactinemia, which ultimately lead to anovulatory infertility. Therefore, with &quot;Tiangui&quot; as the entry point, it is the treatment trend for ovulatory disorders under Yibing Tongzhi.

Long-term oral administration of Epimedii Folium induced cholestasis in mice by interfering with bile acid transport

Ethnopharmacological relevanceEpimedii Folium (EF) is a common traditional Chinese medicine that functions as a tonifying kidney yang to strengthen bones and muscles and dispel wind dampness (limb pain, lethargy, nausea, anorexia, and loose stools). Several studies have reported the potential risk of cholestatic liver damage from EF use; however, there have been few investigations of EF-induced cholestasis, particularly the underlying mechanisms. Aims of the studyThe purpose of this study was to evaluate the risk of EF-induced cholestasis in vivo and to explore the mechanisms of action. Materials and methodsICR mice were orally administered a water extract of EF (WEF) in doses of 6.5 and 19.5 g/kg/day for 14 weeks. Liver-to-body weight ratios, body weight, histopathological examination, and biochemical analyses were performed to assess WEF-induced cholestasis in the mice. Genes associated with bile acid (BA) metabolism and transport, including sodium taurocholate cotransporting polypeptide (NTCP), cytochrome P450 8B1 (CYP8B1), bile-salt export pump (BSEP), multidrug resistance P-glycoproteins 1 (MDR1), and farnesoid X receptor (FXR), were measured at the transcript and protein levels to investigate the potential mechanisms through which cholestasis is aroused by EF. ResultsAfter administration of WEF for 14 weeks, mice in the high-dose WEF group showed poor health with an increased liver-to-body weight ratio as well as higher serum aminotransferase, alkaline phosphatase, direct bilirubin, and total BA levels. Compared with the control group, mRNA expression of NTCP and cholesterol 7a-hydroxylase (CYP7A1) increased, and levels of BSEP, MDR1, multidrug resistance-associated protein 2, and multidrug resistance-associated protein 3 decreased in the WEF-treated group. NTCP, BSEP, MDR1, and CYP8B1 showed similar mRNA and protein expression trends. ConclusionWe demonstrated that the long-term oral administration of WEF causes cholestatic liver injury in mice, which is consistent with reported clinical cases. Furthermore, we found that the destruction of BA metabolism and transport is involved in WEF-induced cholestasis. The fine-scale molecular mechanisms of WEF-induced cholestasis and the active compounds of EF need further study.