Multi-glycoside of Tripterygium wilfordii Hook. f. attenuates glomerulosclerosis in a rat model of diabetic nephropathy by exerting anti-microinflammatory effects without affecting hyperglycemia

Abstract

Multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) has been proven to be clinically effective in relieving microinflammation in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain unclear. In the process of early DN, microinflammation and activation of p38 mitogen-activated protein kinase (MAPK) and canonical nuclear factor (NF)-κB signaling pathways are the important mechanisms by which hyperglycemia contributes to glomerulosclerosis (GS). Therefore, this study aimed to examine the ameliorative effects of GTW on GS, and then to clarify its anti-microinflammatory mechanisms by inhibiting p38 MAPK and NF-κB signaling activities in the kidney. All rats were divided into 4 groups: the sham group, the sham + GTW group, the vehicle group and the GTW group. The suitable dose of GTW and vehicle were daily administered for 8 weeks after the induction of DN by unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The general status of the rats, biochemical parameters, renal histological changes and macrophages in glomeruli, as well as expression of the key proteins in the p38 MAPK and canonical NF-κB signaling pathways and inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and transforming growth factor (TGF)-β1 in the kidney were examined, respectively. The results revealed that, GTW improved the general cond ition and biochemical parameters of the rats, but did not lower blood glucose; GTW attenuated GS and suppressed glomerular microinflammation including the infiltration of ED1+ cells in glomeruli and the protein overexpression of TNF-α, IL-1β and TGF-β1 in the kidney; GTW inhibited the protein overexpression of key signaling molecules of p38 MAPK and canonical NF-κB pathways in the kidney including phosphorylated p38 MAPK, phosphorylated inhibitor protein IκB and NF-κB (p65). On the whole, we expounded that GTW, as a natural regulator in vivo, alleviates GS without affecting hyperglycemia, by exerting anti-microinflammatory effects, including reducing macrophage infiltration in glomeruli, suppressing TNF-α, IL-1β and TGF-β1 overexpression in the kidney and inhibiting p38 MAPK and NF-κB signaling activities.

Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy

“…4 However, the side effects, especially uncontrolled blood glucose or reproductive toxicity restrained the use of these treatments. f., an extract from a Chinese herbal medicine has proven to be clinically effective in relieving microinflammation in patients with early DN.…”

“…f., an extract from a Chinese herbal medicine has proven to be clinically effective in relieving microinflammation in patients with early DN. 4 However, the side effects, especially uncontrolled blood glucose or reproductive toxicity restrained the use of these treatments. As a result, to facilitate the development of effective treatments, it is necessary to understand the molecular mechanism by which inflammation drives DN.…”

Different Doses of <b><i>Tripterygium</i></b> Glycosides in the Treatment of Diabetic Nephropathy: Effects on Blood Lipids

“…In the process of early DN, microinflammation and activation of p38 mitogenactivated protein kinase (MAPK) and canonical nuclear factor-κB (NF-κB) signalling pathways are important mechanisms through which hyperglycaemia contributes to glomerulosclerosis. Wu et al [11] revealed that TG improved the general condition and biochemical parameters of rats, but did not decrease blood glucose; TG attenuated glomerulosclerosis and suppressed glomerular microinflammation including the infiltration of ED1 + cells in glomeruli and the overexpression of TNF-α, IL-1β and TGF-β1 in the kidney. In addition, TG inhibited the overexpression of key signalling molecules of p38 MAPK and canonical NF-κB pathways in the kidney including phosphorylated p38 MAPK, and phosphorylated inhibitor proteins IκB and NF-κB (p65).…”

“…In addition, TG is prepared into granules after dynamic circulatory extraction and concentration by evaporating and spray drying and is also monitored for the absence of contaminants (heavy metals, pesticides, hormones and mycotoxins) prior to formulation. The quality of TG was examined by fingerprint analysis using high-performance liquid chromatography in Jiangsu Province Academy of Chinese Medicine (Nanjing, China [11]. In order to avoid the impact of differences in drug quality, the same batch number was specifically chosen.…”

CZ2HF mitigates β-amyloid 25-35 fragment-induced learning and memory impairment through inhibition of neuroinflammation and apoptosis in rats

“…However, whether cZ2HF is capable of alleviating learning and memory impairment in Alzheimer's disease (Ad) remains to be elucidated. The present study was designed to explore the effect and mechanism of cZ2HF on β-amyloid [25][26][27][28][29][30][31][32][33][34][35] )-induced impairment in the learning and memory of rats. Morris water maze test was used to determine spatial learning and memory ability in Aβ 25-35 -induced Ad rats and hippocampal neuronal damage and apoptosis were observed using hematoxylin and eosin staining, Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively.…”