Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms

Title:Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms

Volume: 17

Author(s): Fengyan Tang, Bo Zhao, Li Zhang, Faisal Raza*, Hajra Zafar, Shao Zhong*, Lin Li, Wenhua Zhu, Lingna Fang, Bing Lu, Liwen Shen, Ping Guo, Nengxing Yu and Quanmin Li*

Affiliation:

• School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China

• Department of Endocrinology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215399, Jiangsu, China

• Department of Endocrinology, PLA Rocket Force Characteristic Medical Center, 100000, Beijing, China

Abstract:

Objective: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated.

Methods: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques.

Results: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin–angiotensin–aldosterone system, and promotion of β-cell sensitivity to insulin.

Conclusion: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Cite this article as:

Tang Fengyan, Zhao Bo, Zhang Li, Raza Faisal*, Zafar Hajra, Zhong Shao*, Li Lin, Zhu Wenhua, Fang Lingna, Lu Bing, Shen Liwen, Guo Ping, Yu Nengxing and Li Quanmin*, Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms, Current Molecular Pharmacology 2024; 17 : e18761429267000 . https://dx.doi.org/10.2174/0118761429267000231004111024