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Saikosaponin d (SSD) alleviates diabetic peripheral neuropathy by regulating the AQP1/RhoA/ROCK signaling in streptozotocin-induced diabetic rats

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Abstract

Aims

Diabetic peripheral neuropathy (DPN) is one of the most important complications of diabetes with a poor prognosis. Saikosaponin d (SSD) is a triterpenoid saponin isolated from Radix Bupleuri that has multiple pharmacological activities. However, whether SSD affects DPN is unclarified.

Methods

Sprague Dawley rats were treated with streptozotocin (STZ) and high-fat diet (HFD) to induce DPN, in the presence or absence of SSD, with or without transfection of lentivirus vectors carrying siRNA targeting aquaporin 1 (si-AQP1). The body weight, plasma glucose levels, mechanical and thermal hyperalgesia, and nerve conductive velocity (NCV) of rats were measured. Hematoxylin–Eosin staining was used for histopathological observation of sciatic nerves. RT-qPCR and western blotting were utilized for measuring expression levels of AQP1 and ras homolog family member A/Rho-associated protein kinase (RhoA/ROCK) signaling pathway-related markers in dorsal root ganglion (DRG) of rats.

Results

SSD increased the body weight, decreased plasma glucose levels, attenuated mechanical and thermal hyperalgesia, enhanced NCV and reduced proinflammatory cytokine levels in DPN rats. AQP1 displayed a high level in DPN rats and SSD treatment repressed the expression of AQP1. SSD enhanced the protective effect of AQP1 knockdown on the pathological changes of DPN. AQP1 depletion suppressed the activation of RhoA/ROCK signaling pathway in DPN rats.

Conclusion

SSD alleviates STZ/HFD-induced DPN in rats by inhibiting the AQP1/RhoA/ROCK signaling pathway.

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Abbreviations

DPN:

Diabetic peripheral neuropathy

SSD:

Saikosaponin d

STZ:

Streptozotocin

HFD:

High-fat diet

DRG:

Dorsal root ganglion

siRNA:

Small interference RNA

AQP1:

Aquaporin 1

RhoA:

Ras homolog family member A

ROCK:

Rho-associated protein kinase

LIMK:

LIM-domain kinase 1

TNF-α:

Tumor necrosis factor alpha

IL-1β:

Interleukin 1beta

IL-6:

Interleukin 6

PWL:

Paw withdrawal threshold

NCV:

Nerve conductive velocity

MNCV:

Motor NCV

SNCV:

Sensory NCV

ELISA:

Enzyme-linked immunosorbent assay

RT-qPCR:

Real-time quantitative polymerase chain reaction

ANOVA:

Analysis of variance

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Acknowledgements

Not applicable.

Funding

The work was supported by Hubei Provincial Health and Health Commission Traditional Chinese Medicine Research Project, Young Talent Project (Approval Number: ZY2021Q037).

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Authors and Affiliations

  1. Department of Geriatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, No. 4, Huayuan Mountain, Wuchang District, Wuhan, 430061, Hubei, China

    Qingwei Xiang & Yu Liu

  2. Department of Obstetrics and Gynecology, Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430061, Hubei, China

    Li Chen

Authors
  1. Qingwei Xiang
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  2. Yu Liu
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  3. Li Chen
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Correspondence to Qingwei Xiang.

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Ethical statement

All animal experiments were conducted following the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals and approved by the Animal Ethics Committee of Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine.

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Xiang, Q., Liu, Y. & Chen, L. Saikosaponin d (SSD) alleviates diabetic peripheral neuropathy by regulating the AQP1/RhoA/ROCK signaling in streptozotocin-induced diabetic rats. Acta Diabetol 60, 805–815 (2023). https://doi.org/10.1007/s00592-023-02060-9

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