2. Academic Validation
  3. Bufotenines-loaded liposome exerts anti-inflammatory, analgesic effects and reduce gastrointestinal toxicity through altering lipid and bufotenines metabolism

Bufotenines-loaded liposome exerts anti-inflammatory, analgesic effects and reduce gastrointestinal toxicity through altering lipid and bufotenines metabolism

  • Biomed Pharmacother. 2022 Sep:153:113492. doi: 10.1016/j.biopha.2022.113492.
Lili Shen 1,  Xiang Lv 1,  Xin Yang 1,  Shuangbing Deng 2,  Lina Liu 3,  Jing Zhou 4,  Yuyu Zhu 5,  Hongyue Ma 6
Affiliations

Affiliations

  • 1 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
  • 2 State Key Laboratory of Innovative Natural Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, Jiangxi 341000, China.
  • 3 The First School of Clinical Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, 210029 Nanjing, China.
  • 4 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China. Electronic address: jingzhou_nj@126.com.
  • 5 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China. Electronic address: 300571@njucm.edu.cn.
  • 6 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China; State Key Laboratory of Innovative Natural Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, Jiangxi 341000, China. Electronic address: hongyuema@njucm.edu.cn.
PMID: 36076586 DOI: 10.1016/j.biopha.2022.113492
Abstract

Bufotenines, a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent, but the potential toxicity limited its clinic use. In this paper, bufotenines-loaded Liposome was prepared and optimized. Then, the therapeutic effects and drug safety of bufotenines-liposome were investigated against inflammation and pain on animal models, with a focus on gastrointestinal toxicity. Bufotenines and its Liposome significantly increased paw withdrawal mechanical threshold (PWMT) in Von Frey test and hot paw withdrawal latency (HPWL) in hot-plate test. Moreover, intestinal absorption in vitro and pathological analysis in vivo showed that total bufotenines-loaded Liposome significantly reduced the gastrointestinal irritation through reducing exposure of total bufotenines on intestinal tissue. High-sensitivity lipidomics analysis revealed the effect of total bufotenines-loaded Liposome were be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX) and Lipoxygenase (LOX), the up-regulation of Cytochrome P450 (CYP450), and Other pathways, thus regulating lipid metabolism pathway and ultimately reducing gastrointestinal irritation. This study shows that liposome-loaded bufotenines has anti-inflammatory, analgesic effects and achieves toxicity reduction. These results provide systematic evidences for efficacy and safety of toad venom active ingredients.

Keywords

Analgesia; Anti-inflammation; Bufotenines; Gastrointestinal irritation; Lipid metabolism; Liposome.

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