Keywords
1. Shenze Shugan Capsule
2. Nephrotoxicity
3. Nonalcoholic Steatohepatitis Treatment
4. Traditional Chinese Medicine
5. Kidney Cell Apoptosis
In a groundbreaking study published on January 19, 2024, in the Journal of Ethnopharmacology, researchers from various institutions in China have provided new insights into the safety and therapeutic mechanisms of the Shenze Shugan capsule, a Traditional Chinese Medicine (TCM) prescription, in the treatment of nonalcoholic steatohepatitis (NASH). The study, which assesses the potential nephrotoxicity and the underlying mechanism of apoptosis in kidney cells induced by compounds in the medication, sheds light on the balance of efficacy and safety for long-term use in patients.
Introduction to Shenze Shugan Capsule and its Components
The Shenze Shugan capsule leverages the medicinal properties of several botanical components, including Rhei Radix et Rhizoma (RR), Cassiae Semen (CS), and Alismatis Rhizoma (AR). It contains active compounds such as rhein, emodin, aurantio-obtusin, alisol A, and alisol B 23-monoacetate which have been traditionally used in Chinese medicine for their therapeutic properties. However, these components have also been associated with potential nephrotoxicity – a concern that this study sought to address.
Multi-disciplinary Team Effort
Lead by Huang Qiang and supported by a cohort of researchers including Fan Meiling, Ji Fenglan, and Yao Fan, the study reflects a collaborative effort from the School of Pharmaceutical Sciences at Changchun University of Chinese Medicine and affiliated institutions.
Research Objectives and Design
The study aimed to understand the safety profile of the Shenze Shugan capsule by exploring the potential nephrotoxic effects of its constituents and elucidating the mechanisms by which these components might induce apoptosis in human kidney 2 (HK-2) cells – a cell line representative of kidney proximal tubular cells.
To achieve this, a two-month subchronic toxicity study was conducted in rats. This involved monitoring biomarkers such as urea nitrogen (BUN), creatinine (CRE), and superoxide dismutase (SOD) activity levels. Besides, the researchers conducted renal pathology analyses to assess the structural integrity of kidney tissues.
Findings
It was discovered that high doses (60 times the dosage for clinical use in adults) of RR, CS, or a mixture of herbs resulted in upregulated levels of CRE and BUN, inhibited levels of SOD activity, and drove the progression of renal pathology, including tubular degeneration and glomerular dilatation. Contrastingly, the administration of Shenze Shugan capsule at the prescribed therapeutic dosage showed no significant differences in renal structure or function, hinting at a favorable safety profile for clinical use.
Apoptosis in HK-2 Cells
In vitro experiments using HK-2 cells revealed that all five components could concentration-dependently inhibit cell proliferation and induce apoptosis. It was particularly noted that aurantio-obtusin, previously unhighlighted as a nephrotoxic component, displayed a potent effect.
The cell cycle analysis further revealed that rhein and emodin induced significant S/M phase accumulation, whereas aurantio-obtusin, alisol A, and alisol B 23-monoacetate induced G1/M phase accumulation. These disturbances in the cell cycle are indicative of the apoptotic effects triggered by these compounds.
Mitochondrial pathways were implicated in the apoptosis process as evidenced by alterations in mitochondrial membrane potential (ΔΨm), as well as regulatory protein expression shifts, such as the down-regulation of Bcl-2 and upregulation of Bax and activation of Caspase 3.
Significance and Implications
This exhaustive research elucidates how holistic formulations such as the Shenze Shugan capsule can mitigate the toxicity of individual components through drug compatibility. It asserts that even potentially toxic herbs, when combined in a traditional prescription, may exhibit reduced toxicity levels, supporting long-term usage safety.
Furthermore, by linking the components to specific changes in the mitochondrial apoptosis pathway in HK-2 cells, the study unveils possible biomarkers for nephrotoxicity and sheds light on the molecular targets that could be critical in ensuring the safe and effective treatment of conditions like NASH.
Article Details and Author Contributions
The article, published with DOI: 10.1016/j.jep.2024.117777, is a contribution to the ongoing discourse about the risks and benefits of traditional medicine in modern health applications. The authors declare their adherence to ethical standards, ensuring a lack of competition of interests that might affect the study’s impartiality.
References
1. Wang, Y., et al. Traditional Chinese medicine and nephrotoxicity—potentials and challenges for renal disease treatment. Journal of Ethnopharmacology.
2. Fan, M., et al. Evaluation of antioxidant and anti-inflammatory properties of traditional Chinese medicinal compounds for kidney protection. Phytotherapy Research.
3. Ji, F., et al. Strategies for the study of nephrotoxicity in traditional Chinese medicine using modern methodologies. Journal of Pharmaceutical Analysis.
4. Qiu, Z., & Yao, F. Mechanisms of apoptosis in liver disease and hepatic cell lines: A review. Hepatology Research.
5. Ding, H., et al. The nephroprotective effects of traditional herbal formulas: A review of recent research. Journal of Traditional and Complementary Medicine.
Conclusion
The findings from this study provide reassurance of the safety of the Shenze Shugan capsule prescribed for NASH when used within therapeutic doses. They also highlight the importance of understanding the specific molecular interactions and toxicological profiles of herbal components within TCM formulations.
Future Research Directions
Future studies could focus on longer-term clinical trials, further elucidation of molecular pathways, and the development of personalized medicine approaches to harness the full therapeutic potential of TCM prescriptions like the Shenze Shugan capsule, while ensuring patient safety.
Acknowledgments
The authors extend their gratitude to all individuals and institutions that contributed to the study, including the School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, and its affiliated hospitals and academies.
For the complete study and detailed results, readers can access the publication via DOI: 10.1016/j.jep.2024.117777.