<br>红果人参果 (HGGG) 通过抑制 NLRP3 炎性体和调节肠道菌群来预防糖尿病肾病的肾损伤,Phytomedicine

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红果人参果 (HGGG) 通过抑制 NLRP3 炎性体和调节肠道菌群来预防糖尿病肾病的肾损伤
Phytomedicine ( IF 6.7 ) Pub Date : 2024-07-06 , DOI: 10.1016/j.phymed.2024.155861
Shu Pan ₁ , Shan-Shan Jiang ₁ , Rui Li ₂ , Bei Tian ₃ , Chun-Yue Huang ₂ , Rong Wang ₁ , Yue-Yue Li ₁ , Hui Zhu ₁ , Yong-Fang Yuan ₁ , Xiao Hu ₂

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糖尿病肾病（DN）是糖尿病最严重的并发症之一，可导致终末期肾功能衰竭，大约三分之一的患者需要透析。 DN目前仍缺乏有效、特异的治疗方法。从天然食品中寻找新药是治疗糖尿病及其并发症的另一种方法。红果人参果 (HGGG) 是一种具有适口性和营养价值的浆果，具有减缓 DN 进展的药用特性。本研究调查了 HGGG 对链脲佐菌素 (STZ) 诱导的大鼠糖尿病肾病 (DN) 的影响，并阐明了其保护肾脏和糖尿病管理益处的机制。 LC-MS 光谱方法鉴定了 HGGG 中的主要成分。为了诱导 DN，雄性 Sprague-Dawley (SD) 大鼠接受单次腹腔注射 75 mg/kg STZ。在八周的治疗期间，我们评估了生化参数，包括血糖、尿白蛋白肌酐比 (UACR)、血尿素氮 (BUN) 和尿 N-乙酰-β-氨基葡萄糖苷酶 (NAG)。使用马森三色、高碘酸希夫 (PAS) 和苏木精 - 伊红 (H&E) 染色剂检查组织病理学。我们使用蛋白质印迹和免疫组织化学分析了促炎介质和组织纤维化程度。通过 16S rDNA 测序来表征肠道微生物群组成。鉴定出 17 种化学化合物，其中洛贝乔林、木犀草素和芦丁被列为主要活性元素。 HGGG 提取物似乎具有肾脏保护作用，UACR、BUN 和尿液 NAG 水平的改善证明了这一点。 HGGG 治疗的 DN 大鼠的肾脏保护作用与肾纤维化的减少和 NLRP3 炎性体的抑制有关。此外，HGGG 给药改善了 DN 大鼠的肠道屏障完整性并改变了肠道微生物群，增加了已知调节多胺和产生短链脂肪酸 (SCFA) 的有益细菌的相对丰度，包括瘤胃球菌、Barnesiella_sp、Anaerovoracaceae 和 Prevotellaceae_NK3B31。同时，HGGG 治疗减少了颤螺菌的存在，颤螺菌是负责产生脂多糖 (LPS) 的潜在病原体。 HGGG 有潜力成为一种有益的水果，通过调节肠道微生物群来控制糖尿病及其相关并发症。

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Hong Guo Ginseng Guo (HGGG) protects against kidney injury in diabetic nephropathy by inhibiting NLRP3 inflammasome and regulating intestinal flora

Diabetic nephropathy (DN) is one of the most serious complications of diabetes which leads to end-stage renal failure and approximately one-third of patients need dialysis. There is still a lack of effective and specific treatment for DN. Searching new drugs from natural foods is an alternative approach to treat diabetes and its complications. Hong Guo Ginseng Guo (HGGG), a berry with palatability and nutritional benefits, has exhibited medicinal properties to mitigate the progression of DN. This study investigates the effects of HGGG on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats and elucidates the mechanisms underlying its reno-protective and diabetes management benefits. The LC-MS spectra method identified the primary ingredients in HGGG. To induce DN, male Sprague-Dawley (SD) rats received a single intraperitoneal injection of 75 mg/kg STZ. Over an eight-week treatment period, we assessed biochemical parameters including blood glucose, urine albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and urine N-acetyl-beta--glucosaminidase (NAG). Tissue pathology was examined using Masson's trichrome, Periodic Acid-Schiff (PAS), and Hematoxylin-Eosin (H&E) stains. We analyzed pro-inflammatory mediators and tissue fibrosis extent using Western blotting and immunohistochemistry. Gut microbiota composition was characterized via 16S rDNA sequencing. Seventeen chemical compounds were identified, with lobetyolin, luteolin, and rutin highlighted as the primary active elements. HGGG extract appeared to confer renal protection, demonstrated by improvements in UACR, BUN, and urine NAG levels. The reno protective effects in HGGG-treated DN rats were linked to reduced renal fibrosis and inhibition of the NLRP3 inflammasome. Additionally, HGGG administration improved gut barrier integrity and altered the gut microbiota in DN rats, increasing the relative abundance of beneficial bacteria known for regulating polyamines and producing short-chain fatty acids (SCFAs), including Ruminococcus, Barnesiella_sp, Anaerovoracaceae, and Prevotellaceae_NK3B31. Meanwhile, treatment with HGGG decreasing the presence of Oscillospira, potential pathogens responsible for producing lipopolysaccharide (LPS). HGGG has potential as a beneficial fruit for managing diabetes and its associated complications through modulation of the gut microbiota.

更新日期：2024-07-06

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