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Changes in 24 h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) levels. * p < 0.05, ** p < 0.01 compared to the immunoglobulin A nephropathy (IgAN) model group. A: Normal, healthy controls; B: IgAN rat models; C: prednisone acetate group (PAG); D: tripterygium glycoside tablet group; E-G: treatment group that received 0.5, 1, and 2 g/kg periostracum cicadae, respectively.
Source publication
Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify n...
Contexts in source publication
Context 1
... molding, urine from rats was collected at 24 h, and it was observed that IgAN rats developed macroscopic hematuresis, however, the normal group and treatment group had no expression. The IgAN rat models showed significantly higher urine protein, blood urea nitrogen (BUN), and serum creatinine (Src) levels than the normal, healthy controls, whereas these were markedly lower in the treatment group (Figure 1). These findings indicate that periostracum cicadae treatment lowers protein, BUN, and creatinine (CREA) levels in the IgAN rat model. ...
Context 2
... 2018, 19, x 3 of 17 Figure 1. Changes in 24 h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) levels. ...
Citations
... Periostracum cicadae (PC), the cast-off shell of the Cryptotympana pustulata Fabricius belonging to the cicadidae, is an animal-based traditional Chinese medicine in Korea and China [10]. PC possess many interesting pharmacological and physiological activities, such as diaphoretic, anti-convulsive, sedative, anti-pyretic, and anti-allergic effects [11,12]. PC is originally described in Ming-I-Pieh-Lu (an ancient Chinese medical book dating to the Han Dynasty), which is used to treat convulsions, the nocturnal crying of children, delirium, and feverish chills [13]. ...
Insomnia is the second most prevalent mental illness worldwide. Periostracum cicadae (PC), as an animal traditional Chinese medicine with rich pharmacological effects, has been documented as a treatment for children’s night cries, and later extended to treat insomnia. This study aimed to investigate the effects of PC extract and N-acetyldopamine compounds in ameliorating insomnia. The UPLC-ESI-QTOF-MS analysis determined that PC extract mainly contained N-acetyldopamine components. Previously, we also isolated some acetyldopamine polymers from PC extract, among which acetyldopamine dimer A (NADA) was present in high content. Molecular docking and molecular dynamic simulations demonstrated that NADA could form stable complexes with 5-HT1A, BDNF, and D2R proteins, respectively. The effects of PC extract and NADA on insomnia were evaluated in the PCPA-induced insomnia model. The results indicated that PC extract and NADA could effectively ameliorate hypothalamic pathology of insomnia rats, increase the levels of 5-HT, GABA, and BDNF, and decrease the levels of DA, DOPAC, and HVA. Meanwhile, the PC extract and NADA also could significantly affect the expression of 5-HT1A, BDNF, and DARPP-32 proteins. This study proved that PC extract and acetyldopamine dimer A could effectively improve PCPA-induced insomnia in rats. It is speculated that the main pharmacological substances of PC were acetyldopamine components.
... SD rats were randomly divided into six groups (n = 8/group), including normal group, model group, Losartan (Los) group, low dose SBDII (SBDII-L) group, medium dose SBDII (SBDII-M) group and high dose SBDII (SBDII-H) group. The IgAN experimental animal model was established by treatment with bovine serum albumin (BSA, Sigma-Aldrich, USA), lipopolysaccharide (LPS, Sigma-Aldrich, USA), and carbon tetrachloride (CCL4, Aladdin, Shanghai, China) [15][16][17], and specific implementation was as follows: BSA (600 mg/kg, gavage every other day), CCL4 (0.1 mL, plus 0.5 mL castor oil, subcutaneous injection once a week) and LPS (0.25 mg/kg, caudal vein injection at week 7, 10 and 13) for 14 weeks. The dosage of herbs were calculated based on the body surface area. ...
Background
IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification.
Method
We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified.
Result
A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt.
Conclusion
This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.
... The SD rats were randomly assigned into three groups of seven, namely, the control (CON), ceftriaxone (Cef ), and ceftriaxone + TAK242 (TAK) groups. All were administered bovine serum albumin (BSA) and carbon tetrachloride (CCl 4 ) by gavage according to the IgAN modeling methods [9][10][11], Briefly, the immunogen BSA was intragastrically administered at a dose of 400 mg/kg once every other day for eight consecutive weeks, and 0.1 mL of CCl 4 with 0.3 mL of castor oil was administered once weekly for eight weeks. According to literature reports about IgAN modeling, the immunogen BSA and CCl4 were administered to increase intestinal immune response and reduce the ability of the liver to clear intestinal toxin, respectively. ...
Objective
Antibiotic treatments are known to disturb gut microbiota, but their effects on the mucosal barrier and extraintestinal diseases are rarely discussed. The aim of this study was to evaluate and visualize the impact of antibiotics on colonic mucus and the microbial community, and to assess whether intestinal dysbacteriosis is involved in the pathogenesis and progression of extraintestinal diseases in vivo.
Materials and Methods
Twenty-one SD rats were randomly assigned into three groups followed by different experimental treatments. The albumin–creatinine ratio, urinary protein and occult blood semi-quantified test were tested. Fecal samples were collected at different time points (0,4, and 12 weeks) for 16S rRNA gene sequencing. Colon and kidney specimens were examined using light microscopy and transmission electron microscopy (TEM) to identify morphological changes.
Results
Ceftriaxone intervention for one week did not cause any symptoms of diarrhea or weight loss, but the alpha and beta diversities of gut microbiota decreased quickly and significantly, a lower Firmicutes/Bacteroidetes (F/B) ratio was observed. At week 12, although the alpha and beta diversities increased to a level similar to that of the control (CON) group, LEfSe analysis indicated that the microbial community composition still differed significantly in each group. In addition, KEGG metabolic prediction revealed different metabolic functions in each group. TEM examination of colon revealed that dramatic morphological changes were observed in the ceftriaxone (Cef) group, wherein microvilli were misaligned and shortened significantly and morphologically intact bacteria were seen on the epithelial cell surface. TEM examination of kidneys from the Cef group showed characteristic glomerular changes in the form of widely irregularly thickened glomerular basement membrane (GBM) and foot process fusion or effacement; mild thickening of the GBM and foot process fusion was detected when ceftriaxone and Resatorvid (TAK242, an inhibitor of TLR4 signaling) are used together in the ceftriaxone + TAK242 (TAK) group.
Conclusions
Short-term use of ceftriaxone induced dynamic changes of gut microbiota and lead to intestinal barrier disruption and ultrastructural changes of kidneys in the SD rats. Moreover, interference with the TLR4-dependent signaling pathway can alleviate the damage to the intestinal barrier and kidney.
... It is composed of six TCMs, including fruits of Prunus mume (Siebold) Siebold & Zucc. All six herbs or their constituents have been reported to have anti-allergic effects [5][6][7][8][9][10] . ...
... The AGC was 1 × 10 3 , and the IT was 50 ms. The data-dependent analysis (DDA) scanning was applied to trigger the second stage fragmentation, which was to select twelve parent ions with the highest intensity at each Tang Ding, et al. / Chin J Nat Med, 2022, 20(x): [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] scanning point of MS 1 as the targeted precursor ions for further MS 2 fragmentation. The dynamic exclusion function was utilized to avoid repetitive ion scans and save analysis time. ...
... RBL-2H3 cells were sensitized overnight with DNP-IgE (100 ng/mL) in 96-well black plates. Cells were then pre-Tang Ding, et al. / Chin J Nat Med, 2022, 20(x): [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] treated with different concentrations of GMK (80, 120 and 160 μg/mL) for 2 h, followed by incubation with prewarmed Hank's buffer containing Fluo-8/Am (5 μM) and Pluronic F-127 (0.04 %) at 37 °C for 30 min. The treated cells were stimulated with DNP-BSA (1 μg/mL) and immediately detected the fluorescence intensity. ...
Guominkang (GMK), a Chinese medicine formula, has been used to treat allergic diseases in clinical settings for many years. To evaluate the anti-allergic effect and molecular mechanism of action of GMK extract, RBL-2H3 cell models and passive cutaneous anaphylaxis (PCA) mouse models were established. High performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analyses were performed to characterize the chemical composition of GMK. A total of 94 compounds were identified or tentatively identified from GMK. Three of them, emodin, ursolic acid, and hamaudol, were the first time to be identified as potential active compounds in GMK, since they inhibited the degranulation of mast cells. The anti-allergic effect of hamaudol was the first to be discovered. GMK could markedly mitigate the shade of Evans Blue extravasation and ear incrassation in PCA mouse models. Additionally, GMK significantly inhibited the degranulation of mast cells, suppressed mast cell degranulation by reducing Ca2 + influx and the levels of TNF-α, IL-4, and histamine, and markedly inhibited the phosphorylation of Lyn, Syk, PLCγ1, IκBα, and NF-κB p65. Molecular docking results indicated that hamaudol and emodin had strong interaction with FcεRI and NF-κB related proteins, while ursolic acid only interacted with NF-κB associated proteins. These results suggest GMK suppresses the activation of MCs both in vivo and in vitro. The mechanism underlying its anti-allergic activity is associated with the inhibition of FcεRI and NF-κB pathways.
... In IgAN rats, Periostracum cicadae could result in the reduction of the levels of TNF-α, IL-1β, and IL-6 in serum. [63] In addition, treated with hirudin, the expression of fibrosis indexes in IgAN rat kidney, included TGF-β1, collagen-IV, and fibronectin-1, was remarkably suppressed. [64] Schisandrin B therapy significantly increased the expression of cytoplasmic p65 and NF-κB in LPS-induced HK-2 cells. ...
... In the last decades, several natural medicinal monomers have been widely used in the treatment of IgAN and are known to regain the balance of immune function, [55][56][57][58][59] regulate the expression of inflammatory factors, [61][62][63][64][65] and inhibit the proliferation of GMCs. [67][68][69] Among these, the Terpenoid lactones extracted from TwHF have been widely used as an alternative to immunosuppressive medications for the treatment of primary glomerular disease. ...
IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.
... SD rats were randomly divided into three groups, the Control, IgAN, and CTSS inhibitor groups with 10 rats in each group. A rat model of IgAN was induced as described previously (9,10). Briefly, SD rats were randomized and administrated with bovine serum albumin (BSA, 100 mg/ml in distilled water, 4 ml/kg, B2064, Sigma, St. Louis, USA) every other days by gavage for eight consecutive weeks and injected subcutaneously with 0.1 ml of CCl4 dissolved in 0.5 ml castor oil weekly for nine consecutive weeks as well as injected intravenously with 50 µg Lipopolysaccharide (LPS, L2880, Sigma) in saline at the 6th and 9th week post induction. ...
Objective: Cathepsin S (CTSS) is an important lysosomal cysteine protease. This study aimed at investigating the clinical significance of CTSS and underlying mechanism in immunoglobulin A nephropathy (IgAN).
Methods: This study recruited 25 children with IgAN and age-matched controls and their serum CTSS levels were measured by enzyme-linked immunosorbent assay (ELISA). Following induction of IgAN in rats, their kidney CTSS expression, IgA accumulation and serum CTSS were characterized by immunohistochemistry, immunofluorescence, and ELISA. The impact of IgA1 aggregates on the proliferation of human mesangial cells (HMCs) was determined by Cell Counting Kit-8 and Western blot analysis of Ki67.
Results: Compared to the non-IgAN controls, significantly up-regulated CTSS expression was detected in the renal tissues, particularly in the glomerular mesangium and tubular epithelial cells of IgAN patients, accompanied by higher levels of serum CTSS ( P < 0.05), which were correlated with the levels of 24-h-urine proteins and microalbumin and urine erythrocytes and grades of IgAN Lee's classification in children with IgAN ( P < 0.01 for all). Following induction of IgAN, we detected inducible IgA accumulation and increased levels of CTSS expression in the glomerular mesangium and glomerular damages in rats, which were mitigated by LY3000328, a CTSS-specific inhibitor. Treatment with LY3000328 significantly mitigated the Ki67 expression in the kidney of IgAN rats ( P < 0.01) and significantly minimized the IgA1 aggregate-stimulated proliferation of HMCs and their Ki67 expression in vitro ( P < 0.01).
Conclusions: CTSS promoted the proliferation of glomerular mesangial cells, contributing to the pathogenesis of IgAN and may be a new therapeutic target for intervention of aberrant mesangial cell proliferation during the process of IgAN.
... Recent studies have shown that the CP has inhibitory effects on Th17 differentiation [6], allergic rhinitis [7], anaphylactic reactions [8], and contact dermatitis [36]. The CP improved kidney inflammation and fibrosis in IgA nephropathy rat models by reducing MCP-1, TNFα, IL-1β, and IL-6 levels [37]. Chang et al. [38] reported that the CP inhibited oxidative stress and inflammation in keratinocytes. ...
... The CP is a commonly used crude drug in traditional medicine. Based on preliminary studies [1,8,37,[55][56][57][58] and including our supplementary data ( Figures S1 and S2, Table S1), which showed the safety of CP and OA, safe and effective concentrations were used in the current study. Thus, our results indicate that CP and OA have the potential for use in the treatment of patients with allergic asthma. ...
Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.
... Following that, the model rats, whose 24-h urinary protein levels were higher than those of the normal rats, were randomly divided into two groups (eight rats per group)-IgAN model group and ZWT treatment group (16.8 g/kg). Rats in the control and model groups were administered 10 ml/kg/d saline using the oral gavage method (Bai et al., 2019b;Liu et al., 2017a;Yang et al., 2018). Drug treatments were performed by administering the corresponding drugs once daily for 4 weeks Li et al., 2020). ...
Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.
... 81 The administration of PC significantly reduces TLR4, TGF-b1, MCP-1, and IgA expression in the IgAN rats. 82 N-acetyldopamine dimer from Chan Tui inhibits ROS generation, NO production, and NF-kB activity and the expression of proinflammatory molecules such as iNOS, IL-6, TNF-a, and COX-2 in LPS-induced RAW264.7 cells. 83 Huang Bo (Cortex Phellodendri) approaches for eczema that include herbal internal supplements, bath additives, and creams or ointments (remedies A-C). ...
Objective
To summarize the recent evidence of traditional Chinese medicine (TCM) for food allergy and eczema.
Data Sources
Published literature from PubMed database and abstract conference presentations.
Study Selections
Studies relevant to TCM for food allergy and eczema were included.
Results
TCM is the main component of complementary and alternative medicine in the US. Food Allergy Herbal Formula 2 (FAHF-2) (derived from classical formula Wu Mei Wan) prevented systemic anaphylaxis in murine models and showed safety and preliminary immunomodulatory effects on T cells and basophils. Phase II trial of combined TCM with OIT and Omalizumab for multiple food allergy is ongoing. Retrospective practice-based evidence study showed that comprehensive TCM therapy effectively prevented frequent and severe food anaphylaxis triggered by skin contact or protein inhalation. The traditional Japanese herbal medicine Kakkonto suppressed allergic diarrhea and decreased mast cells in intestinal mucosa in a murine model. Active compounds from TCM showed potent inhibition of IgE, mast cell activation and pro-inflammatory cytokines/signaling pathway (TNF-α, IL-8, NF-kB) suggesting value for both IgE and non-IgE mediated food allergy. Triple TCM Therapy including ingestion, bath, and cream markedly improved skin lesion, itching, sleep loss in patients with corticosteroid dependent, recalcitrant, or topical steroid withdrawal. Xiao Fang San and Japanese, Korean formulas showed effectiveness in eczema. Acupuncture reduced wheal size, skin itching, basophil activation in atopic dermatitis. TCM are generally safe.
Conclusion
TCM has potential as safe and effective therapy for food allergy and eczema. Further research is needed for botanical drug development and for further define the mechanisms of actions.
... A total of 2 weeks after the injection of BSA into the footpads, 6 mmol/l hydrochloric acid-acidified water containing 0.1% BSA was administered every other day. Blood was drawn after three immunization injections of BSA, and the serum anti-BSA antibody titer was measured using the double immunodiffusion method (28). When the antibody titer reached 1:16, 3 mg BSA was intraperitoneally injected daily. ...
The aim of the present study was to investigate the involvement of B cell‑activating factor (BAFF) in the pathogenesis of IgA nephropathy by activating the tumor necrosis factor receptor‑associated factor 6 (TRAF6)/NF‑κB signaling pathway in glomerular mesangial cells. For the clinical analysis, blood, urine and kidney tissue samples were collected from 58 patients diagnosed with primary IgA nephropathy by renal biopsy. For the in vitro study, glomerular mesangial cells were divided into five groups: Control (con)‑short hairpin RNA (shRNA) (control group); con‑shRNA + BAFF (20 ng/ml); con‑shRNA + BAFF + BAFF‑RFc chimera protein (500 µg/ml); TRAF6‑shRNA; and TRAF6‑shRNA + BAFF (20 ng/ml). For the in vivo experiments, 60 Sprague‑Dawley rats were randomly divided into four groups: Con‑small interfering RNA (siRNA) (control group); con‑siRNA + IgA (IgA nephropathy group), BAFF‑RFc chimera protein (2 µg/ml) + IgA, and TRAF6‑siRNA (0.2 µM) + IgA. Reverse transcription‑quantitative PCR was performed to evaluate the mRNA expression levels of TRAF6, connective tissue growth factor (CTGF), fibronectin (FN) and NF‑κBP65. Western blot analysis was used to detect the protein expression levels of TRAF6, FN, CTGF and phosphorylated‑NF‑κBP65 in glomerular mesangial cells and kidney tissues. The results revealed that plasma BAFF levels were positively correlated with the severity of pathological damage in patients with IgA nephropathy. In vitro, BAFF induced the mRNA and protein expression of TRAF6, CTGF, FN and NF‑κBP65 in glomerular mesangial cells. After the BAFF‑RFc chimera protein was added to inhibit the binding of BAFF and BAFF‑receptor (‑R), this effect was reduced. In vivo, inhibition of the effects of BAFF via injection with the BAFF‑R Fc chimera protein reduced kidney damage in rats suffering from IgA nephropathy. The effect on the expression of signaling pathway‑associated proteins was also alleviated. In conclusion, BAFF enhanced the expression of fibroblast factors in the kidneys by activating the TRAF6/NF‑κB signaling pathway.
