Search JIM Advanced Search

Journal of Integrative Medicine ›› 2021, Vol. 19 ›› Issue (2): 135-143.doi: 10.1016/j.joim.2020.12.005

• Original Experimental Research • Previous Articles     Next Articles

Genome-wide analysis of hippocampal transfer RNA-derived small RNAs identifies new potential therapeutic targets of Bushen Tiansui formula against Alzheimer’s disease

Zhe-yu Zhanga,1, Chun-hu Zhangb,1, Jing-jing Yangb, Pan-pan Xua, Peng-ji Yia, Mu-li Huc, Wei-jun Penga   

  1. a. Department of Integrated Traditional Chinese & Western Medicine, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
    b. Department of Integrated Traditional Chinese & Western Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
    c. Department of Scientific Research, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, Chin
  • Received:2019-12-23 Accepted:2020-03-25 Online:2021-03-12 Published:2020-12-12
  • Contact: Wen-jun Peng


Bushen Tiansui formula (BSTSF), a traditional Chinese medicine prescription, has been widely used to treat Alzheimer’s disease (AD). However, the mechanisms underlying its effects remain largely unknown. In this study, a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs (tsRNAs) in the hippocampus, to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs, a novel small non-coding RNA.


To generate a validated AD model, oligomeric amyloid-β1-42 (Aβ1-42) was injected intracerebroventricularly into rats. The Morris water maze (MWM) test was used to evaluate rat cognitive performance, and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus. Potential targets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs.


The learning and memory deficits of Aβ1–42-induced AD rats, assessed by MWM tests, were clearly ameliorated by BSTSF treatment. A total of 387 tsRNAs were detected in the rat hippocampus. Among them, 13 were significantly dysregulated in AD rats compared with sham control rats, while 57 were markedly altered by BSTSF treatment, relative to untreated AD rats (fold change ≥ 2 and P < 0.05). Moreover, six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR. Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles, via multiple signaling pathways and Gene Ontology biological functions, including cyclic adenosine monophosphate and retrograde endocannabinoid signaling.


This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ1–42-induced AD rats, demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.

Key words: Traditional Chinese medicine, Alzheimer’s disease, Endocannabinoids, Hippocampus, Small non-coding RNAs, Transfer RNA

[1] Wan-jun Guo, Yi Wang, Yu Deng, Lin-yan Cheng, Xin Liu, Ruo-fan Xi, Sheng-jie Zhu, Xin-yi Feng, Liang Hua, Kan Ze, Jian-yong Zhu, Dong-jie Guo, Fu-lun Li. Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61. Journal of Integrative Medicine, 2022, 20(4): 376-384.
[2] Shang-jin Song, Xuan Liu, Qing Ji, Da-zhi Sun, Li-juan Xiu, Jing-yu Xu, Xiao-qiang Yue. Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression. Journal of Integrative Medicine, 2022, 20(4): 355-364.
[3] Marisa Casal. Improving the health and treatment success rates of in vitro fertilization patients with traditional chinese medicine: need for more robust evidence and innovative approaches. Journal of Integrative Medicine, 2022, 20(3): 187-192.
[4] Ning Guo, Fei Wu, Mei Wu, Yuan Wang, Qing Lang, Xiao Lin, Yi Feng. Progress in the design and quality control of placeboes for clinical trials of traditional Chinese medicine . Journal of Integrative Medicine, 2022, 20(3): 204-212.
[5] Yan-jun Lin, Kun-li Jiao, Bo Liu, Lu Fang, Shu Meng. Antiplatelet and myocardial protective effect of shexiang tongxin dropping pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial. Journal of Integrative Medicine, 2022, 20(2): 126-134.
[6] Jia-jia Li, Qing Liang, Guang-chun Sun. Traditional Chinese medicine for prevention and treatment of hepatocellular carcinoma: A focus on epithelial-mesenchymal transition. Journal of Integrative Medicine, 2021, 19(6): 469-477.
[7] Rui-jin Qiu, Min Li, Jia-yuan Hu, Jing Chen, Hong-cai Shang. Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine. Journal of Integrative Medicine, 2021, 19(5): 389-394.
[8] Mao-xing Pan, Chui-yang Zheng, Yuan-jun Deng, Kai-rui Tang, Huan Nie, Ji-qian Xie, Dong-dong Liu, Gui-fang Tu, Qin-he Yang, Yu-pei Zhang. Hepatic protective effects of Shenling Baizhu powder, a herbal compound, against inflammatory damage via TLR4/NLRP3 signalling pathway in rats with nonalcoholic fatty liver disease . Journal of Integrative Medicine, 2021, 19(5): 428-438.
[9] Ning Zhang, Xiao-he Xiao. Integrative medicine in the era of cancer immunotherapy: Challenges and opportunities. Journal of Integrative Medicine, 2021, 19(4): 291-294.
[10] Thomas Efferth, An-long Xu, Roxana Damiescu, Mita Banerjee, Norbert W. Paul, David Y.W. Lee. Can eastern wisdom resolve western epidemics? Traditional chinese medicine therapies and the opioid crisis. Journal of Integrative Medicine, 2021, 19(4): 295-299.
[11] Si-qi Tang, Yun-liang Wang, Zi-ye Xie, Yang Zhang, Yi Guo, Kang-li Gao, Tang-you Mao, Chun-e Xie, Jun-xiang Li, Xiao-yan Gao. Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome. Journal of Integrative Medicine, 2021, 19(3): 274-281.
[12] Miao-yan Shi, Shi-qi Sun, Wei Zhang, Xing Zhang, Gui-hua Xu, Xuan Chen, Zi-jian Su, Xiu-ming Song, Lu-jiong Liu, Yi-bao Zhang, Yi-le Zhang, Meng Sun, Qi Chen, Yan Xue, Hua Lü, Wei-an Yuan, Xiao-rong Chen, Yun-fei Lu. Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: a retrospective cohort study. Journal of Integrative Medicine, 2021, 19(3): 226-231.
[13] Shu-jun Wei, Qing-man He, Qing Zhang, Kang-hua Fu, Ruo-lan Li, Wei Peng, Yong-xiang Gao. Traditional Chinese medicine is a useful and promising alternative strategy for treatment of Sjogren's syndrome: A review. Journal of Integrative Medicine, 2021, 19(3): 191-202.
[14] Yi Xia, Lu-shao-bo Shi, Jing-hui Chang, Hua-zhang Miao, Dong Wang. Impact of the COVID-19 pandemic on intention to use traditional Chinese medicine: A cross-sectional study based on the theory of planned behavior. Journal of Integrative Medicine, 2021, 19(3): 219-225.
[15] Na Zhi, Qian Mo, Shuo Yang, Yuan-xing Qin, Hao Chen, Zeng-guang Wu, Cai-hong Lan, Jun Zhang, Yin-long Li. Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report. Journal of Integrative Medicine, 2021, 19(2): 185-190.
Full text



[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278