Jinlida Granules Improve Dysfunction of Hypothalamic-Pituitary-Thyroid Axis in Diabetic Rats Induced by STZ

Abstract

Objective We aim to explore the effects and mechanisms of Jinlida granules on the dysfunction of hypothalamic-pituitary-thyroid (HPT) axis in diabetic rats induced by streptozotocin. Methods A total of 48 SD rats were randomized into normal control group (NC, n = 6) and diabetic group (n = 42). Rats in diabetic group were randomly divided into diabetes mellitus (DM) control group, low, medium, and high doses of Jinlida group (JL, JM, and JH), medium dose of Jinlida plus Tongxinluo group (JM + T), metformin group (Met), and Saxagliptin group (Sax) (n = 6 in each group). Diabetic rats were obtained by intraperitoneal injection of streptozotocin and sacrificed at 8 weeks to examine the function of HPT axis. Results Levels of fasting blood glucose (P < 0.05), pIκB, TNFα (P < 0.05), pNF-κB, and IL-6 (P < 0.01) in liver tissue and TSHR mRNA expression (P < 0.01) in diabetic group were significantly increased, while levels of serum T3 and T4, thyroid hormone receptor (TR) mRNA and Dio1 mRNA in liver tissue, and sodium iodide symporter (NIS) mRNA in thyroid tissue in diabetic group were significantly decreased compared with those in NC group (P < 0.01). Among diabetic groups, level of fasting blood glucose in JH, JM + T and Met group was lower (P < 0.05) compared with DM group. However, levels of serum T3 and T4, TR mRNA in liver tissue, TSHR, and NIS mRNA in thyroid tissue in JH, JM + T, Met, and Sax group were significantly increased (P < 0.01) compared to DM group. In contrast, levels of Dio1 mRNA, pI-κB in Met and JM + T groups, pNF-κB in JH, JM + T, and Met group, and TNFα and IL-6 in JM, JH, JM + T, and Met group were significantly decreased (P < 0.05). HE staining showed reduced thyroid follicular epithelium and follicular area, as well as increased colloid area in DM group, indicating impaired synthesis, reabsorption, and secretory of TH in diabetes, which was significantly improved in JH, JM + T, and Met groups. Conclusion HPT axis dysfunction in DM could be significantly improved by Jinlida granules. The mechanism might be associated with the anti-inflammatory effects involving NF-κB pathway. Our findings suggested the potential benefit of Jinlida granules for patients with HPT axis dysfunction and DM, which was to be verified by more experimental and clinical studies.

TSH Combined with TSHR Aggravates Diabetic Peripheral Neuropathy by Promoting Oxidative Stress and Apoptosis in Schwann Cells

“…The potential mechanism for this observation may involve low thyroid function. Further, the relatively low levels of thyroid hormones in DC mice possibly resulted in decreased thyroglobulin levels, hence the decrease in the inhibition of TSHR transcription [ 46 ]. Second, autoimmunity has been identified as the primary etiology of thyroid-dysfunction-associated DM [ 47 , 48 ].…”

Comparative efficacy and safety of traditional Chinese patent medicine for the treatment of type 2 diabetes mellitus

“…Pharmacological investigations indicated that TCPMs present beneficial effects on reducing body weight, enhancing insulin sensitivity, protecting β-cells, improving insulin secretion, correcting glucose and lipid metabolism disorders, and improving the microcirculation and the immune system. [ 5 6 7 8 9 10 11 12 13 ] For example, the Tianmai Xiaoke tablet which contains of Schisandra Chinensis, Ophiopogon Japonicus, Trichosanthis Radix and Chromium Picolinate is approved by the State Food and Drug Administration of China (state medical license number Z20049007) can decrease FBG and HbA1c levels in T2DM patients. [26] In addition, some studies demonstrated that Tianmai Xiaoke tablets could down-regulate PTP1B and PCK2 by activating the insulin signaling pathway, thereby reducing the HbA1c level in diabetic rats.…”

“…Many traditional Chinese patent medicine (TCPMs) are used as adjuvant drugs combined with conventional Western medicine therapy in the treatment of T2DM, including Jinlida granule, Xiaoke pill, Shenqi Jiangtang granule, Jinqi Jiangtang Tablet, Tianmai Xiaoke tablet, etc. [ 5 6 7 8 9 10 11 12 13 14 ] Besides, relevant treatment guidelines also highlight the important role of TCPMs (e.g., Jinlida granule) against this disease. [15] However, a direct comparison of the efficacy and safety of different TCPMs for the treatment of T2DM is lacked, which affects the optimal choice of the clinical treatment plan.…”

Integrating Evidence of the Traditional Chinese Medicine Collateral Disease Theory in Prevention and Treatment of Cardiovascular Continuum

“…Regarding these overlapped key nodes of the cardiovascular continuum, there are TCM set prescriptions based on collateral disease that could offer intervention targets at various continuum stages ( Figure 1 ). For example, Jinlida granules (JLDG) for metabolic syndrome, Tongxinluo (TXL) for atherosclerotic plaque and myocardial protection, Shensongyangxin (SSYX) capsules for anti-arrhythmias via metabolic reconstruction, and Qiliqiangxin (QLQX) capsules for cardiac remodeling and heart failure have been recognized under the guidance of translational medicine ( Table 1 ) ( Bai et al, 2013 ; Wang et al, 2014 ; Zaki et al, 2014 ; Luan et al, 2015 ; Wang et al, 2015 ; Zhang et al, 2016 ; Fan et al, 2017 ; Shen et al, 2017 ; Zhao et al, 2017 ; Chen H. et al, 2018 ; Chen Y. et al, 2018 ; Gao et al, 2018 ; Wang et al, 2018 ; Zhang et al, 2018 ; Lyu et al, 2019 ; Tung et al, 2019 ; Zhou et al, 2019 ; Cheng W. et al, 2020 ; Li et al, 2020 ; Yang et al, 2020 ; Zhao et al, 2020 ; Jiang et al, 2021 ; Hao et al, 2022 ). These set prescriptions have been approved for by the Chinese National Medical Products Administration (NMPA), and broadly used in clinical practice in the Chinese community.…”