Effects and mechanisms of Chinese herbal medicine on IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN), is the main cause of end-stage renal disease, that causes serious physical and psychological burden to patients worldwide. Some traditional treatment measures, such as blocking the renin-angiotensin-aldosterone system, controlling blood pressure, and following a low-protein diet, may not achieve satisfactory results. Therefore, more effective and safe therapies for IgAN are urgently needed. PURPOSE: The aim of this review is to summarize the clinical efficacy of Chinese herbal medicines (CHMs) and their active ingredients in the treatment and management of IgAN based on the results of clinical trials, systematic reviews, and meta-analyses, to fully understand the advantages and perspectives of CHMs in the treatment of IgAN. STUDY DESIGN AND METHODS: For this review, the following electronic databases were consulted: PubMed, ResearchGate, Science Direct, Web of Science, Chinese National Knowledge Infrastructure and Wanfang Data, "IgA nephropathy," "traditional Chinese medicine," "Chinese herbal medicine," "herb," "mechanism," "Meta-analysis," "systematic review," "RCT" and their combinations were the keywords to search the relevant literature. Data were collected from 1990 to 2022. RESULTS: This review found that the active ingredients of CHMs commonly act on multiple signaling pathways in the clinical treatment of IgAN, mainly with antioxidant, anti-inflammatory and anti-fibrosis effects, and regulation of autophagy. CONCLUSION: Compared with the single-target therapy of modern medicine, CHMs can regulate the corresponding pathways from the aspects of anti-inflammation, anti-oxidation, anti-fibrosis and autophagy to play a multi-target treatment of IgAN through syndrome differentiation and treatment, which has good clinical efficacy and can be used as the first choice or alternative therapy for IgAN treatment. This review provides evidence and research direction for a comprehensive clinical understanding of the protective effect of Chinese herbal medicine on IgAN.

Mechanism for the therapeutic effect of Tripterygium wilfordii Hook. f. preparations on IgA nephropathy. / é›·å ¬è—¤åˆ¶å‰‚æ²»ç–—IgAè‚¾ç— çš„ä½œç”¨æœºåˆ¶.

Tripterygium wilfordii Hook. f. is a traditional Chinese herbal medicine. The bioactive compounds from Tripterygium wilfordii Hook. f. have unique immunosuppressive and anti-inflammatory effects, and can exert their pharmacological effects through multi-target and multi-channel. Tripterygium wilfordii Hook. f. preparations have been used in IgA nephropathy (IgAN) for many years and are well accepted for good curative effects. However, the underlying mechanisms are still unclear. It is valuable to summarize the current progress in clinical application of Tripterygium wilfordii Hook. f. preparations in IgAN and other kidney diseases. We discussed the component characteristics, efficacies in reducing urinary protein levels and protecting renal function, as well as the side effects. As for the mechanisms, we should focus on all links of IgAN pathogenesis, including reducing the production of pathogenic IgA, decreasing renal inflammation and fibrosis, and protecting podocytes. As a representative drugs with clear efficacy and potential toxicity, Tripterygium wilfordii Hook. f. preparations need more in-depth basic and clinical research to improve their efficacy and safety.

Clinicopathological features, diagnosis, and treatment of IgA nephropathy with minimal change disease related to exposure to mercury-containing cosmetics: a case report
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AIM: Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream. MATERIAL AND METHODS: The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period. RESULTS AND CONCLUSIONS: The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
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TJN-259 improves mesangial lesions in experimental immunoglobulin A nephropathy in ddY mice.

TJN-259 is a chemical substance based on the structural features of the botanically derived ingredient acteoside. This study was performed in order to elucidate the antinephritic effects of TJN-259 in experimental immunoglobulin A (IgA) nephropathy. In this study, 28-week-old ddY mice were used as a spontaneous model of IgA nephropathy. With regard to spontaneous IgA nephropathy, we investigated the effects of TJN-259 administered from 28 to 40 weeks. In addition, an accelerated model of IgA nephropathy was experimentally induced in ddY mice by oral administration of bovine serum albumin, followed by reticuloendothelial blocking by colloidal carbon injection and heminephrectomy. At 10 weeks after the 3rd carbon injection, we also examined the effects of TJN-259 on accelerated IgA nephropathy. To investigate the effects of TJN-259 on transforming growth factor (TGF)-beta1 production in accelerated IgA nephropathy, kidneys were isolated and measured TGF-beta1 by the enzyme-linked immunosorbent assay (ELISA) method. The administration of TJN-259 to mice with spontaneous IgA nephropathy decreased the incidence of mesangial expansion as well as the number of nuclei per glomerular cross-section in comparison with that of non-treated mice. In addition, TJN-259 treatment prevented the increase in the incidence of mesangial expansion, crescent formation, and segmental sclerosis in glomeruli in accelerated IgA nephropathy. TJN-259 also inhibited the increased immunostaining score of collagen type IV and TGF-beta1 in glomeruli of accelerated IgA nephropathy. Treatment with TJN-259 inhibited the increases in renal total and mature TGF-beta1 protein levels in accelerated type IgA nephropathy. TJN-259 failed to inhibit the increase in serum IgA levels in both models. These results suggest that TJN-259 was an effective treatment against IgA nephropathy in ddY mice, acting via the suppression of TGF-beta1 production in glomeruli.

Cholestatic jaundice and IgA nephropathy induced by OTC muscle building agent superdrol.

Over the counter (OTC) medicines are commonly used in the United States despite a lack of scientific evidence for clinical utility and toxicity associated with their use. A case of jaundice and IgA nephropathy as a consequence of use of a muscle enhancing OTC supplement that was advertised as innocuous with no hormonal activity is described. IgA nephropathy has not been described previously in association with the use of testosterone. The case highlights that, besides adulteration, the misrepresentation of chemicals present in OTC medications and supplements can create confusion and a false sense of security with their use.

Attenuation of mycotoxin-induced IgA nephropathy by eicosapentaenoic acid in the mouse: dose response and relation to IL-6 expression.

Clinical trials have revealed that progression of immunoglobulin A nephropathy (IgAN), the most common form of human glomerulonephritis, is inhibited by dietary (n-3) polyunsaturated fatty acid (PUFA) supplementation. The early stages of IgAN can be mimicked by feeding mice the mycotoxin deoxynivalenol (DON). Here, the effects of consuming the (n-3) PUFA eicosapentaenoic acid (EPA) on DON-induced IgAN were assessed relative to dose dependency and to expression of interleukin (IL-6). In the dose-response study, weight gain and feed intake did not differ among mice consuming 20 ppm DON supplemented with 0%, 0.1%, 0.5% and 3% EPA for 16 weeks. Mice fed the two highest EPA concentrations exhibited markedly increased splenic EPA, docosapentaenoic acid and docosahexaenoic acid, whereas arachidonic acid was decreased in all three EPA fed groups. Deoxynivalenol consumption significantly increased serum IgA and IgA immune complexes as well as kidney mesangial IgA deposition. All three IgAN markers were attenuated in mice fed 3% EPA diet but not in those fed 0.1% or 0.5% EPA. Elevated IgA production was observed in spleen and Peyer's patch (PP) cell cultures derived from mice fed DON in control diets, but this was reduced in cultures from mice fed 0.1%, 0.5% and 3% EPA. Acute DON exposure increased serum levels of IL-6, a cytokine that drives differentiation of IgA-committed B cells to IgA secretion. Relatedly, expression of IL-6 mRNA and IL-6 heteronuclear RNA, a marker of IL-6 transcription, was increased in spleen and PP. All three indicators of IL-6 expression were suppressed in mice consuming 3% EPA. Suppressed IL-6 corresponded to decreased binding activity of two factors that regulate transcription of this cytokine, cyclic AMP response element-binding protein and activator protein-1. The results indicate that a threshold existed for EPA relative to suppression of experimental IgAN and that the threshold dose was effective at inhibiting IL-6 transcription.

Deoxynivalenol-induced mitogen-activated protein kinase phosphorylation and IL-6 expression in mice suppressed by fish oil.

The trichothecene mycotoxin deoxynivalenol (DON) induces IgA hyperelevation and mesangial IgA deposition in mice that mimics the early stages of human IgA nephropathy (IgAN). Among potential mediators of this disease, interleukin-6 (IL-6) is likely to play a particularly critical role in IgA elevation and disease exacerbation. Based on previous findings that dietary fish oil (FO) suppresses DON-induced IgAN, we hypothesized that FO inhibits the induction of IL-6 expression by this mycotoxin in vivo and in vitro. Mice were fed modified AIN 93G diet amended with 7% corn oil (CO) or with 1% corn oil plus 6% menhaden fish oil (FO) for up to 8 weeks and then exposed acutely to DON by oral gavage. DON-induced plasma IL-6 and splenic mRNA elevation in FO-fed mice were significantly suppressed after 8 weeks when compared to the CO-fed group. The effects of FO on phosphorylation of mitogen-activated protein kinases (MAPKs), critical upstream transducers of IL-6 up-regulation, were also assessed. DON-induced phosphorylation of extracellular signal regulated protein kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) was significantly suppressed in spleens of mice fed with FO, whereas p38 was not. Splenic COX-2 mRNA expression, which has been previously shown to enhance DON-induced IL-6, was also significantly decreased by FO, whereas plasma levels of the COX-2 metabolite, prostaglandin E2, were not affected. To confirm in vivo findings, the effects of pretreatment with the two primary n-3 PUFAs in FO, eicosapentaenoic acid (20:5[n-3]; EPA) and docosahexaenoic acid, (22:6[n-3]; DHA), on DON-induced IL-6 expression were assessed in LPS-treated RAW 264.7 macrophage cells. Consistent with the in vivo findings, both EPA and DHA significantly suppressed IL-6 superinduction by DON, as well as impaired DON-induced ERK1/2 and JNK1/2 phosphorylation. In contrast, the n-6 PUFA arachidonic acid (20:4[n-3]) had markedly less effects on these MAPKs. Taken together, the capacity of FO and its component n-3 PUFAs to suppress IL-6 expression as well as ERK 1/2 and JNK 1/2 activation might explain, in part, the reported suppressive effects of these lipids on DON-induced IgA nephropathy.

[The effect of the extract from Radix Paeoniae alba on IgA Glomerulonephritis in mice].

OBJECTIVE: To observe the effect of the extract from Radix Paeoniae Alba on IgA glomerulonephritis in mice. METHODS: IgA glomerulonephritis was induced by injection of dextran and sephadex-150. After administrating the extract, the contents of urinary protein, BUN and Cr in serum were determined. RESULTS: The extract could inhibit the decline of mouse weight, and decrease urinary protein content and BUN content in serum. While, the extract had no effect on Cr in serum. CONCLUSION: The extract from Radix Paeoniae Alba had therapeutical effect on IgA glomerulonephritis.

Deoxynivalenol-induced IgA production and IgA nephropathy-aberrant mucosal immune response with systemic repercussions.

Dietary exposure to the common foodborne mycotoxin deoxynivalenol (DON) selectively upregulates serum immunoglobulin A (IgA) in the mouse, most of which is polymeric, thus suggesting that the mucosal immune system is a primary target. When ingested, DON has no adjuvant or antigen properties but, rather, induces polyclonal IgA synthesis and serum elevation in an isotype-specific fashion. Resultant hyperelevated IgA is polyspecific, autoreactive and is likely to be involved in immune complex formation as well as kidney mesangial deposition. These latter effects mimic IgA nephropathy, the most common human glomerulonephritis. At the cellular level, DON upregulates production of T helper cytokines and enhances T cell help for IgA secretion. Analogous effects are observed in the macrophage with IL-6 being of particular importance based on ex vivo reconstitution and antibody ablation studies as well as experiments with IL-6 deficient mice. Upregulation of cytokines by DON involves both increased transcriptional activation and mRNA stability which are mediated by activation of mitogen-activated protein kinases. Interestingly, dietary omega-3 fatty acids can downregulate these processes and ameliorate DON-induced IgA nephropathy. From the perspective of gut mucosal immunotoxicology, these studies demonstrate that the capacity of a chemical to affect mucosal immune response can have systemic repercussions and, further, that these effects can be modulated by an appropriate nutritional intervention.

Inhibition of activated human mesangial cell proliferation by the natural product of Cordyceps sinensis (H1-A): an implication for treatment of IgA mesangial nephropathy.

Cordyceps sinensis (CS) is a parasitic fungus that has been used as a Chinese medicine for a long time in the treatment of nephritis. Today, the hypothesis about the pathogenesis of immunoglobulin A nephropathy (IgAN) is that nephritogenic IgA immune complexes (IgAIC) go to the kidney to stimulate resting mesangial cells to release cytokines and growth factors. These cytokines and growth factors cause mesangial cell proliferation and release matrix, chemical mediators that lead to the glomerular injury. However, nephritogenic IgAIC in humans is still unknown. To solve this problem previously, we established an in vitro model that showed that cultured human mesangial cells (HMC) stimulated with interleukin-1 (IL-1) plus IL-6 can cause mesangial cell proliferation, increasing production of chemical mediators and superoxide anion. An in vivo model also proved that this culture medium may lead to renal injury with hematuria and proteinuria. Therefore, to fractionate the crude components that can be used in the treatment of patients with IgAN, we cultured HMC, and then an HMC activating model with HMC incubated with IL-1 and IL-6 was established. We fractionated the crude methanolic extracts from fruiting bodies of CS with the use of this in vitro inhibition of HMC activation model as our assay method. In brief, the fruiting bodies were extracted by silica gel column chromatography. One out of 6 column fractions, F-2, significantly inhibited the HMC activation by IL-1 plus IL-6. The acute toxicity test with male Institute of Cancer Research mice showed no liver toxicity or mutagenicity. Then we established an IgAN animal model with R36A (Pneumococcal C-polysaccharide purified from Streptococcus pneumoniae) as antigen and anti-R36A IgA monoclonal antibody to form nephritogenic IgA-IC, which can induce hematuria and proteinuria in mice with IgA deposition in the mesangial area. The mice in the IgAN model fed with 1% F-2 in diet had significant reduction of hematuria and proteinuria together with histopathologic improvement. Therefore this fraction was then purified by silica gel column chromatography and high-performance liquid chromatography, which got a purified compound H1-A, which can suppress the activated HMC and alleviate IgAN (Berger's disease) with clinical and histologic improvement. These results give us a new regimen for the treatment of patients with IgAN in the future.