Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats

Abstract

ObjectiveInflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN.Research Design and MethodsProtective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined.ResultsWe found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7.ConclusionsThe present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.

Diverse Role of TGF-β in Kidney Disease

“…Asperulosidic acid, a bioactive iridoid glycoside, can also exert renal protective effects by inactivating both TGF-β/Smad and NF-κB signaling pathways (Xianyuan et al, 2019). Similar therapeutic effects are also found in other studies with herbal medicines (Nie et al, 2014;Wan et al, 2014;Zhao et al, 2016). Targeting Smad3-dependent non-coding RNAs could be another therapeutic approach to treat renal fibrosis and inflammation (Figure 4c).…”

Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway

“…TS formula is produced from six types of traditional Chinese medicine, namely Astragalus, Radix puerariae, Lucid ganoderma, Ligustrum lucidum, Rheum officinale and Salvia miltiorrhiza. Astragalus and Radix puerariae (15). Astragalus is beneficial for supplementing Qi and strengthening the immune system (36).…”

“…Chinese medicinal treatment applies multi-channel and multi-target activities to achieve positive and effective therapeutic effects, thus the application of traditional Chinese medicine has great potential in the prevention of DN. According to the traditional Chinese medicine theory of Professor Kefu Chai, it is believed that the basic pathogenesis of early-and medium-stage DN is the deficiency of both Qi and Yin, which results in blood stasis (15). Previous results have indicated that a Chinese herbal compound prescription, Tangshen (TS) formula, has demonstrated good clinical efficacy in managing early-stage DN, as it is believed in traditional Chinese medicine that it supplements Qi, nourishes Yin, improves blood flow and removes obstructions in the blood vessels (16).…”

Chinese herbal medicine Tangshen Formula Treatment For Type 2 Diabetic Kidney Disease in Early Stage : study protocol for a randomized controlled trial

“…In modern times, Many patients have turned to Chinese herbal medicine for treatment as a complementary and basic combinationdrug therapy for kidney disease in China due to its fewer adverse reactions and more effective interventions. Currently, a research from Taiwan has demonstrated that patients with CKD who used CHM had a significantly reduced ESRD risk (60%) [46].Relevant clinical observations have shown that TSF appears to prevent further development and deterioration of the disease, which includes the reduction of urinary albumin and the normalization of glomerular filtration rate [47][48][49][50].Potential mechanisms have been proved that herbal medicine could regulate oxidative stress which is well recognized that oxidative stress plays a major role in worsening of DKD [50][51][52].However, there is less clinical research on delaying the progression of DKD, especially in the early stage as only period of reversing kidney lesion. This work has the potential function to delay the development of DKD.…”