Component analysis and antiasthmatic effects of Huashanshen dripping pill

  • Shuli ManEmail author
  • Nina Cui
  • Xuanshuo Liu
  • Long Ma
  • Changxiao Liu
  • Wenyuan GaoEmail author
Original Research


Huashanshen dripping pill (HSS), a commonly used traditional Chinese medicine, has been widely used in China due to its properties of antiasthma, expectorant, and antitussive. However, it was less in-depth understanding of the chemical composition, their absorption in plasma and potential biological mechanism. In this research, ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was developed to simultaneously identify the chemical constituents and absorption in rat plasma after oral administration of HSS. IgE-sensitized to ovalbumin was induced in BALB/c mice. ELISA and molecular docking analysis were carried out to identify their antiasthmatic mechanisms. As a result, 11 compounds were tentatively characterized by comparing the retention time, ion fragments, and the accurate mass measurement of [M + H]+ ions in the HSS. Two alkaloids including d-anisodamine and l-anisodamine were identified in the rat plasma after oral administration of HSS. The pills alleviated airway inflammation in lung tissues, and inhibited IgE, IL-4, and IL-5 in the serum. Furthermore, there were several amino acid residues involved in anisodamine-targeting receptors of hydrogen bonds and hydrophobic interactions via molecular docking indication. All in all, anisodamine would be the main component in the HSS whose antiasthmatic effects based on the inhibition of IgE, IL-4, and IL-5 production.


Huashanshen dripping pill Traditional Chinese medicine UHPLC-QTOF-MS Molecular docking Anisodamine Asthma 





enzyme-linked immunosorbent assay


huashanshen dripping pill


immunoglobulin E




mass spectrometry




the retention time


ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry



This work was supported by grants 81673647, 81673535, and 81503086 from the National Natural Science Foundation of China.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Cooper AM, Hobson PS, Jutton MR, Kao MW, Drung B, Schmidt B, Fear DJ, Beavil AJ, McDonnell JM, Sutton BJ, Gould HJ (2012) Soluble CD23 controls IgE synthesis and homeostasis in human B cells. J Immunol 188:3199–3207CrossRefGoogle Scholar
  2. Delescluse I, Mace H, Adcock JJ (2012) Inhibition of airway hyper-responsiveness by TRPV1 antagonists (SB-705498 and PF-04065463) in the unanaesthetized, ovalbumin-sensitized guinea pig. Br J Pharm 166:1822–1832CrossRefGoogle Scholar
  3. Dhaliwal B, Yuan D, Pang MO, Henry AJ, Cain K, Oxbrow A, Fabiane SM, Beavil AJ, McDonnell JM, Gould HJ, Sutton BJ (2012) Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcepsilonRI. Proc Natl Acad Sci USA 109:12686–12691CrossRefGoogle Scholar
  4. Foster PS, Maltby S, Rosenberg HF, Tay HL, Hogan SP, Collison AM, Yang M, Kaiko GE, Hansbro PM, Kumar RK, Mattes J (2017) Modeling TH 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunol Rev 278:20–40. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Hall S, Agrawal DK (2014) Key mediators in the immunopathogenesis of allergic asthma. Int Immunopharmacol 23:316–329CrossRefGoogle Scholar
  6. Holdom MD, Davies AM, Nettleship JE, Bagby SC, Dhaliwal B, Girardi E, Hunt J, Gould HJ, Beavil AJ, McDonnell JM, Owens RJ, Sutton BJ (2011) Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor FcvarepsilonRI. Nat Struct Mol Biol 18:571–576CrossRefGoogle Scholar
  7. Hirose K, Iwata A, Tamachi T, Nakajima H (2017) Allergic airway inflammation: key players beyond the Th2 cell pathway. Immunological Rev 278:145–161CrossRefGoogle Scholar
  8. Kistemaker LE, Bos IS, Menzen MH, Maarsingh H, Meurs H, Gosens R (2016) Combination therapy of tiotropium and ciclesonide attenuates airway inflammation and remodeling in a guinea pig model of chronic asthma. Respir Res 17:13CrossRefGoogle Scholar
  9. Kohnen-Johannsen KL, Kayser O (2019) Tropane alkaloids: chemistry, pharmacology, biosynthesis and production. Molecules 24:E796CrossRefGoogle Scholar
  10. Kruse RL, Vanijcharoenkarn K (2018) Drug repurposing to treat asthma and allergic disorders: progress and prospects. Allergy 73:313–322CrossRefGoogle Scholar
  11. Matucci A, Vultaggio A, Maggi E, Kasujee I (2018) Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res 19:113CrossRefGoogle Scholar
  12. Pelaia G, Canonica GW, Matucci A, Paolini R, Triggiani M, Paggiaro P (2017) Targeted therapy in severe asthma today: focus on immunoglobulin E. Drug Des Devel Ther 11:1979–1987CrossRefGoogle Scholar
  13. Pennington LF, Tarchevskaya S, Brigger D, Sathiyamoorthy K, Graham MT, Nadeau KC, Eggel A, Jardetzky TS (2016) Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange. Nat Commun 7:11610CrossRefGoogle Scholar
  14. Steinke JW, Borish L (2001) Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res 2:66–70CrossRefGoogle Scholar
  15. Verbout NG, Jacoby DB, Gleich GJ, Fryer AD (2009) Atropine-enhanced, antigen challenge-induced airway hyperreactivity in guinea pigs is mediated by eosinophils and nerve growth factor. Am J Physiol Lung Cell Mol Physiol 297:L228–L237CrossRefGoogle Scholar
  16. Verbout NG, Lorton JK, Jacoby DB, Fryer AD (2007) Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 292:L1126–L1135CrossRefGoogle Scholar
  17. Wang YH, Zeng KW (2019) Natural products as a crucial source of anti-inflammatory drugs: recent trends and advancements. J Tradit Chin Med 4:257–268Google Scholar
  18. Xu GN, Yang K, Xu ZP, Zhu L, Hou LN, Qi H, Chen HZ, Cui YY (2012) Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility. Toxicol Appl Pharm 262:70–79CrossRefGoogle Scholar
  19. Xu ZP, Wang H, Hou LN, Xia Z, Zhu L, Chen HZ, Cui YY (2011) Modulatory effect of anisodamine on airway hyper-reactivity and eosinophilic inflammation in a murine model of allergic asthma. Int Immunopharmacol 11:260–265CrossRefGoogle Scholar
  20. Zhou M, Ma X, Sun J, Ding G, Cui Q, Miao Y, Hou Y, Jiang M, Bai G (2017) Active fragments-guided drug discovery and design of selective tropane alkaloids using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry coupled with virtual calculation and biological evaluation. Anal Bioanal Chem 409:1145–1157CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of BiotechnologyTianjin University of Science and TechnologyTianjinChina
  2. 2.The State Key Laboratories of Pharmacodynamics and PharmacokineticsTianjinChina
  3. 3.Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and TechnologyTianjin UniversityTianjinChina

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