Assessment of acute toxicity and antitumor efficacy of Shizao decoction

doi:10.5246/jcps.2024.04.025

Journal of Chinese Pharmaceutical Sciences ›› 2024, Vol. 33 ›› Issue (4): 329-338.DOI: 10.5246/jcps.2024.04.025

• Original articles • Previous Articles Next Articles

Assessment of acute toxicity and antitumor efficacy of Shizao decoction

Liwei Ma¹^,², Zhe Chen³, Guoshan Shi⁴, Yujing Wang⁵, Song Chen⁵, Shiyu Ni⁶, Jing Li⁷, Pengling Ge², Jicheng Liu¹^,^*()

¹ Qiqihar Medical University, Medical Sciences Institution (Postdoctoral workstation) Qiqihar 161006, Heilongjiang, China
² Heilongjiang University of Chinese Medicine, Postdoctoral mobile station, Harbin 150040, Heilongjiang, China
³ Qiqihar Medical University, School of Public Health, Qiqihar 161006, Heilongjiang, China
⁴ Guizhou University of Traditional Chinese Medicine, School of Basic Medical Sciences, Guiyang 550025, Guizhou, China
⁵ Qiqihar Medical University, School of Pharmacy, Qiqihar 161006, Heilongjiang, China
⁶ The fifth affiliated hospital of Qiqihar Medical University, Daqing 163001, Heilongjiang, China
⁷ The third affiliated hospital of Qiqihaer Medical University, Qiqihar 161099, Heilongjiang, China

Received:2023-11-04 Revised:2023-11-24 Accepted:2024-01-12 Online:2024-04-30 Published:2024-04-30
Contact: Jicheng Liu
Supported by:
National Natural Science Foundation of China (Grant No. 82174207), the Science and Technology Project of Guizhou Province (Qiankehe Foundation-ZK [2021] General 502), the Growth Project of Young Scientific and Technological Talents in General Colleges and Universities in Guizhou Province (Qianjiaohe KY [2021] 208), and the Qiqihar Science and Technology Bureau Joint Guide Project (Grant No. LHYD-202028).

Abstract

Abstract:

This study aimed to assess the acute toxicity of Shizao decoction (SZD) in KM mice and its antitumor activity, offering insights into drug safety and antitumor efficacy. In experiments, specific pathogen-free (SPF) KM mice were administered either saline (as a blank control) or SZD, and the half-lethal dose (LD₅₀) was determined. Additionally, SPF-grade SD rats were treated with SZD to produce SZD-medicated serum (SZD-MS). Assays, including the MTT method, lactic dehydrogenase (LDH) release, colony formation, and flow cytometry, were utilized to measure the inhibitory effects on cancer cell proliferation and induction of apoptosis. The toxicity tests revealed that none of the mice died after oral administration of SZD, rendering it impossible to establish an LD₅₀ value. Notably, serum biochemistry results significantly diverged from those of the blank control group (P < 0.05). Histopathology, using hematoxylin and eosin (H&E) staining, unveiled that SZD exerted detectable damage on the liver and kidneys of the mice. In terms of antitumor activity, SZD-MS demonstrated a significant inhibition of proliferation in five tumor cell lines when compared to the vehicle control (P < 0.05, P < 0.01). This finding was further supported by the increased LDH release from H22 cells (P < 0.05), a reduction in colony formation (P < 0.05, P < 0.01), and an elevated apoptosis rate (P < 0.01). In conclusion, the study revealed that the maximum oral dosage of SZD, set at 0.8 mL/d for each mouse (roughly 120 times the standard adult daily dose), presented minimal toxicity. Moreover, it possessed promising anti-ascite tumor activity, suggesting its safety and therapeutic potential.

Key words: Shizao decoction, Acute toxicity, Proliferation inhibition, Antitumor activity

Supporting:

Liwei Ma, Zhe Chen, Guoshan Shi, Yujing Wang, Song Chen, Shiyu Ni, Jing Li, Pengling Ge, Jicheng Liu. Assessment of acute toxicity and antitumor efficacy of Shizao decoction[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(4): 329-338.

Figures/Tables 10

Table 1. Effects of SZD on body weight in mice (x ± s, n = 8).

Table 2. Effects of SZD on organ coefficients in mice ((x ± s, n = 8).

Table 3. Effects of SZD on ALT, AST, Cr, and BUN contents in mice serum ((x ± s, n = 8).

Table 4. Effects of SZD-MS on cellular proliferation in 4T1, A549, HepG2, H22 and MCF-7 cells ((x ± s, n = 6).

Table 5. Effects of SZD-MS on LDH content in H22 cell ((x ± s, n = 3).

Table 6. Effects of SZD-MS on colony-forming efficiency in H22 cells ((x ± s, n = 3).

Table 7. Effects of SZD-MS on apoptosis rate in H22 cells ((x ± s, n = 3).

References 20

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Assessment of acute toxicity and antitumor efficacy of Shizao decoction

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