Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
BMC Complement Altern Med. 2018 May 11;18(1):156. doi: 10.1186/s12906-018-2221-x.
Oxidative stress and renal apoptosis play a significant role in the progression of diabetic nephropathy. The tubers of Pueraria tuberosa (Roxb. ex Willd.) DC. has been traditionally used as anti-ageing and health promotive tonic. The purpose of this study was to investigate its nephroprotective effect and mechanism via antioxidant and antiapoptotic potential in Streptozotocin-induced diabetic nephropathy (DN) in rats.
The chemical composition of aqueous extract of Pueraria tuberosa (PTY-2r) was analyzed by gas chromatography-mass spectrometry (GC-MS). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (55 mg/kg body weight) in rats. After 60 days, the rats were randomly divided into 3 groups (n = 6/each group), namely DN control (DN) group-2, DN rats treated with PTY-2r at the dose of 50 mg/100 g, group-3 and 100 mg/100 g, group-4 p.o. for 20 days. The normal rats were chosen as a normal control (NC) group-1. PTY-2r was orally given to the rats for 20 days. Reactive oxygen species (ROS), lipid peroxidation (LPO) and the activity of ROS-scavenging enzymes - superoxide dismutase (SOD), catalase (CAT) & glutathione peroxidase (GPx) were determined in the kidney tissue of DN rats. The expression of apoptosis-related proteins was measured by immunofluorescence.
GC-MS analysis of PTY-2r indicated the presence of 37 compounds among them 5-Hydroxymethylfurfural (17.80%), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (17.03%), n-Hexadecanoic acid (5.18%) and 9-Octadecenoic acid (Z) - (6.69%) were found in the higher amount. A significant increase in ROS and LPO was observed along with the decreased activity of antioxidant enzymes, responsible for oxidative stress in the kidney of DN rats. Since, high oxidative stress induces apoptosis in target cells, as shown by significantly decreased expression of Bcl-2 along with increased expression of Bax, active Caspase-3 & cleaved PARP-1 in DN control rats, suggesting apoptosis. The PTY-2r treatment significantly raised the activity of antioxidant enzymes, suppressed oxidative stress and apoptosis thus, prevented urinary albumin excretion in a dose-dependent manner.
The findings suggest that PTY-2r exerted the nephroprotective potential against STZ induced DN rats via suppressing oxidative stress and apoptosis due to the presence of different bioactive compounds. ᅟ.
氧化应激和肾细胞凋亡在糖尿病肾病的进展中起着重要作用。野葛的块根历来被用作抗衰老和促进健康的滋补品。本研究旨在通过抗氧化和抗细胞凋亡作用，探讨其在链脲佐菌素诱导的糖尿病肾病（DN）大鼠中的肾脏保护作用及其机制。
采用气相色谱-质谱联用（GC-MS）分析野葛水提物（PTY-2r）的化学成分。用链脲佐菌素（STZ）（55mg/kg 体重）腹腔注射诱导糖尿病。60 天后，将大鼠随机分为 3 组（每组 6 只），即糖尿病对照组（DN）组-2、PTY-2r 剂量为 50mg/100g 的组-3 和 100mg/100g 的组-4，po 给药 20 天。正常大鼠作为正常对照组（NC）组-1。PTY-2r 连续 20 天给大鼠灌胃。测定 DN 大鼠肾组织中活性氧（ROS）、脂质过氧化（LPO）和 ROS 清除酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性。免疫荧光法测定细胞凋亡相关蛋白的表达。
PTY-2r 的 GC-MS 分析表明，其中 37 种化合物中，5-羟甲基糠醛（17.80%）、2,3-二氢-3,5-二羟基-6-甲基-4H-吡喃-4-酮（17.03%）、正十六烷酸（5.18%）和 9-十八碳烯酸（Z）-（6.69%）含量较高。DN 大鼠肾组织中 ROS 和 LPO 显著增加，抗氧化酶活性降低，导致氧化应激。由于高氧化应激诱导靶细胞凋亡，DN 对照组大鼠 Bcl-2 表达明显降低，Bax、活性 Caspase-3 和 cleaved PARP-1 表达增加，提示凋亡。PTY-2r 治疗可显著提高抗氧化酶活性，抑制氧化应激和凋亡，从而以剂量依赖的方式防止尿白蛋白排泄。
研究结果表明，PTY-2r 通过抑制氧化应激和凋亡发挥其对 STZ 诱导的糖尿病肾病大鼠的肾脏保护作用，这归因于不同生物活性化合物的存在。
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