Download PDF
Planta Med 2020; 86(10): 665-673
DOI: 10.1055/a-1151-5138
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Total Alkaloids from Menispermum dauricum against Airway Inflammation in Asthmatic Mice

Le Lv‡
1   Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xiʼan, China
2   Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xiʼan, China
,
Bing Yin‡
1   Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xiʼan, China
2   Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xiʼan, China
,
Ye You
1   Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xiʼan, China
2   Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xiʼan, China
,
Zhongyang Sun
1   Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xiʼan, China
2   Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xiʼan, China
,
Jiao He
1   Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xiʼan, China
2   Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xiʼan, China
,
Yan Jun Cao
1   Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xiʼan, China
2   Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xiʼan, China
› Author AffiliationsSupported by: Teaching Research and Achievement cultivation Project of Northwestern University JX18131
Supported by: Young Talent fund of University Association for Science and Technology in Shaanxi, China 20180306
Supported by: Opening Foundation of Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education ZSK2018001
Supported by: Northwest University Graduate Innovation and Creativity Funds YZZ17159
Supported by: National Natural Science Foundation of China 81773870
Further Information

Publication History

received 23 December 2019
revised 13 March 2020

accepted 29 March 2020

Publication Date:
04 May 2020 (online)

Also available at
    Permissions and Reprints

Abstract

Menispermum dauricum is widely used to treat respiratory inflammation, including laryngopharyngitis, tonsillitis, tracheitis, and bronchitis. Total alkaloids isolated from M. dauricum have shown a variety of beneficial bioactivities. However, available data on the effects of M. dauricum total alkaloids against allergic asthma has not been reported. In present study, the protective effect of M. dauricum total alkaloids was evaluated by using an ovalbumin-induced in vivo model of asthma. The asthma model was prepared by sensitizing and challenging mice with ovalbumin, and M. dauricum total alkaloids (100, 200, and 400 mg/kg) were administrated to asthmatic mice by gavage. Histopathological analysis of pulmonary changes was detected by hematoxylin and eosin, and periodic acid-schiff staining. Inflammatory cell counts were determined in bronchoalveolar lavage fluid. Total immunoglobulin E and ovalbumin-specific immunoglobulin E levels in serum, and T-helper 2 cytokines and chemokine levels in bronchoalveolar lavage fluid were detected by an ELISA. Histological results demonstrated that M. dauricum total alkaloids significantly attenuated pulmonary inflammation in asthmatic mice. M. dauricum total alkaloid treatment exhibited marked effects on asthmatic mice in reducing inflammatory cell counts, decreasing interleukin-4, interleukin-5, and interleukin-13 concentrations, and downregulating TNF-α and eotaxin levels in bronchoalveolar lavage fluid. In addition, M. dauricum total alkaloids could also inhibit the elevated serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. These findings confirmed that M. dauricum total alkaloids could suppress airway inflammation in ovalbumin-induced asthma through regulating the T-helper 2 response and chemokine level. M. dauricum total alkaloids may be a potential ethnopharmacological agent for asthmatic patients.

Key words

Menispermum dauricum - Menispermaceae - asthma - inflammation - Th2 cytokine - chemokine
 

  • References

  • 1 Gater A, Nelsen L, Fleming S, Lundy JJ, Bonner N, Hall R, Marshall C, Staunton H, Krishnan JA, Stoloff S, Schatz M, Haughney J. Assessing asthma symptoms in adolescents and adults qualitative research supporting development of the asthma daily symptom diary. Value Health 2016; 19: 440-450
    CrossrefPubMedSearch in Google Scholar
  • 2 Croisant S. Epidemiology of asthma: prevalence and burden of disease. Adv Exp Med Biol 2014; 795: 17-29
    PubMedSearch in Google Scholar
  • 3 Levine SJ, Wenzel SE. Narrative review the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes. Ann Intern Med 2010; 152: 232-237
    PubMedSearch in Google Scholar
  • 4 Moral VP, Donaire JG. Inhaled therapy in asthma. Med Clin (Barc) 2016; 146: 316-323
    CrossrefPubMedSearch in Google Scholar
  • 5 Rodriguez JM, Monsalves-Alvarez M, Henriquez S, Llanos MN, Troncoso R. Glucocorticoid resistance in chronic diseases. Steroids 2016; 115: 182-192
    CrossrefPubMedSearch in Google Scholar
  • 6 Chinese Pharmacopoeia Commission. Pharmacopoeia of the Peopleʼs Republic of China, Volume 1. Beijing: China Medical Science and Technology Publishing Co.; 2015
    Search in Google Scholar
  • 7 Zhang Y, Sun C, Guan QC, Yang JW, Zhao JY. Research of anti-inflammatory and analgesic effect of rhizoma of Menispermum dauricum . Mod Pharm Clin 2009; 24: 367-368
    PubMedSearch in Google Scholar
  • 8 Xing XJ. Pharmacological effects and clinical applications of Menispermum dauricum . J Modern Med Health 2008; 24: 2983-2984
    PubMedSearch in Google Scholar
  • 9 Su Q, Sun C, Zhao WN, Sun WJ. RP-HPLC simultaneous determination of 5 alkaloids in Rhizoma Menispermi. Chin J Pharm Anal 2012; 32: 962-965
    PubMedSearch in Google Scholar
  • 10 Su Q. Studies on the chemical constituents and anti-ulcerative colitis activity of Menispermum dauricum [dissertation]. Xiʼan: Northwest University; 2013
    PubMedSearch in Google Scholar
  • 11 Ma LL, Chu W, Huang AL, Li MC. Inhibitory effect of the compound preparation of traditional Chinese medine on metronidazole-resistant trichomonas vaginalis. Mod Prevent Med 2014; 41: 3765-3767
    PubMedSearch in Google Scholar
  • 12 Liu XH, Han FL. Antiarrhythmic effect of total alkaloid injection of rhizomes of Menispermum dauricum DC. on experimental arrhythmias. Heilongjiang Med J 2000; 13: 160-162
    PubMedSearch in Google Scholar
  • 13 Shan BE, Liu DQ, Liang WJ, Zhang J, Li QX. The anti-tumor effect and immunoregulatory activity of PE2 from Rhizoma Menipermi extracts in vivo . Carcinogen Teratogen Mutagen 2006; 18: 351-354
    PubMedSearch in Google Scholar
  • 14 Li M. Current status of studies on Menispermum dauricum DC. Foreign Med Sci 2005; 27: 267-271
    PubMedSearch in Google Scholar
  • 15 Lambrecht BN, Hammad H. The immunology of asthma. Nature Immunol 2015; 16: 45-56
    CrossrefPubMedSearch in Google Scholar
  • 16 Mauad T, Bel EH, Sterk P. Asthma therapy and airway remodeling. J Allergy Clin Immunol 2007; 120: 997-1009
    CrossrefPubMedSearch in Google Scholar
  • 17 Barnes PJ. Glucocorticosteroids for asthma: From genes to the clinic. NeuroImmune Bio 2007; 7: 359-381
    PubMedSearch in Google Scholar
  • 18 Bui TT, Piao CH, Song CH, Shin HS, Chai OH. Bupleurum chinense extract ameliorates an OVA-induced murine allergic asthma through the reduction of the Th2 and Th17 cytokines production by inactivation of NFκB pathway. Biomed Pharmacother 2017; 91: 1085-1095
    CrossrefPubMedSearch in Google Scholar
  • 19 Inam A, Shahzad M, Shabbir A, Shahid H, Shahid K, Javeed A. Carica papaya ameliorates allergic asthma via down regulation of IL-4, IL-5, eotaxin, TNF-α, NF-κB, and iNOS levels. Phytomed 2017; 32: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 20 Shieh YH, Huang HM, Wang CC, Lee CC, Fan CK, Lee YL. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. Intern Immunopharmacol 2015; 24: 383-391
    CrossrefPubMedSearch in Google Scholar
  • 21 Wei Y, Luo QL, Sun J, Chen MX, Liu F, Dong JC. Bu-Shen-Yi-Qi formulae suppress chronic airway inflammation and regulate Th17/Treg imbalance in the murine ovalbumin asthma model. J Ethnopharmacol 2015; 164: 368-377
    CrossrefPubMedSearch in Google Scholar
  • 22 Zhao YL, Cao J, Shang JH, Liu YP, Afsar K, Wang HS, Qian Y, Liu L, Ye M, Luo XD. Airways antiallergic effect and pharmacokinetics of alkaloids from Alstonia scholaris . Phytomed 2017; 27: 63-72
    CrossrefPubMedSearch in Google Scholar
  • 23 Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov 2013; 12: 1-23
    CrossrefPubMedSearch in Google Scholar
  • 24 Coyle AJ, Ackerman SJ, Burch R, Proud D, Irvin CG. Human eosinophil granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation. J Clin Invest 1995; 95: 1735-1740
    CrossrefPubMedSearch in Google Scholar
  • 25 Redington AE, Howarth PH. Airway wall remodelling in asthma. Thorax 1997; 52: 310-312
    CrossrefPubMedSearch in Google Scholar
  • 26 Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P. Eosinophilic inflammation in asthma. N Engl J Med 1990; 323: 1033-1039
    CrossrefPubMedSearch in Google Scholar
  • 27 Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Wilkins HJ, Henkel T, Nair P. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011; 184: 1125-1132
    CrossrefPubMedSearch in Google Scholar
  • 28 Liu L, Yang J, Huang Y. Human airway smooth muscle cells express eotaxin in response to signaling following mast cell contact. Respiration 2006; 73: 227-235
    CrossrefPubMedSearch in Google Scholar
  • 29 Suzuki T, Arakawa H, Mizuno T, Muramatsu K, Tadaki H, Takizawa T, Mochizuki H, Tokuyama K, Matsukura S, Morikawa A. Differential regulation of eotaxin expression by dexamethasone in normal human lung fibroblasts. Am J Respir Cell Mol Biol 2008; 38: 707-714
    CrossrefPubMedSearch in Google Scholar
  • 30 Pease JE, Williams TJ. Eotaxin and asthma. Curr Opin Pharmacol 2001; 1: 248-253
    CrossrefPubMedSearch in Google Scholar
  • 31 Paplińska M, Hermanowicz-Salamon J, Nejman-Gryz P, Białek-Gosk K, Rubinsztajn R, Arcimowicz M, Placha G, Gora J, Chazan R, Grubek-Jaworska H. Expression of eotaxins in the material from nasal brushing in asthma, allergic rhinitis and COPD patients. Cytokine 2012; 60: 393-399
    CrossrefPubMedSearch in Google Scholar
  • 32 Mazzarella G, Bianco A, Catena E, De Palma R, Abbate GF. Thl/Th2 lymphocyte polarization in asthma. Allergy 2000; 55 (Suppl. 61) 6-9
    PubMedSearch in Google Scholar
  • 33 Liu JT, Xiong HZ, Cheng Y, Cui CD, Zhang X, Xu L, Zhang XM. Effects of taraxasterol on ovalbumin-induced allergic asthma in mice. J Ethnopharmacol 2013; 148: 787-793
    CrossrefPubMedSearch in Google Scholar
  • 34 Perkins C, Wills-Karp M, Finkelman FD. IL-4 induces IL-13-independent allergic airway inflammation. J Allergy Clin Immunol 2006; 118: 410-419
    CrossrefPubMedSearch in Google Scholar
  • 35 Yosri H, Elkashef WF, Said E, Gameil NM. Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. Int Immunopharmacol 2017; 50: 305-312
    CrossrefPubMedSearch in Google Scholar
  • 36 Zhang FQ, Han XP, Zhang F, Ma X, Xiang D, Yang XM, Ou-Yang H, Li ZK. Therapeutic efficacy of a co-blockade of IL-13 and IL-25 on airway inflammation and remodeling in a mouse model of asthma. Int Immunopharmacol 2017; 46: 133-140
    CrossrefPubMedSearch in Google Scholar
  • 37 Brightling C, Berry M, Amrani Y. Targeting TNF-alpha a novel therapeutic approach for asthma. J Allergy Clin Immunol 2008; 121: 5-10
    CrossrefPubMedSearch in Google Scholar
  • 38 Choi IW, Sun K, Kim YS, Ko HM, Im SY, Kim JH, You HJ, Lee YC, Lee JH, Park YM, Lee HK. TNF-alpha induces the late-phase airway hyperresponsiveness and airway inflammation through cytosolic phospholipase A (2) activation. J Allergy Clin Immunol 2005; 116: 537-543
    CrossrefPubMedSearch in Google Scholar
  • 39 Samitas K, Delimpoura V, Zervas E, Gaga M. Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma current knowledge and future perspectives. Eur Respir Rev 2015; 24: 594-601
    CrossrefPubMedSearch in Google Scholar
  • 40 Shida K, Hachimura S, Ametani A, Ishimori M, Ling M, Hashiguchi M, Ueda Y, Sato T, Kumagai Y, Takamizawa K, Habu S, Kaminogawa S. Serum IgE response to orally ingested antigen A novel IgE response model with allergen-specific T-cell receptor transgenic mice. J Allergy Clin Immunol 2000; 105: 788-795
    CrossrefPubMedSearch in Google Scholar
  • 41 Froidure A, Mouthuy J, Durham SR, Chanez P, Sibille Y, Pilette C. Asthma phenotypes and IgE responses. Eur Respir J 2016; 47: 304-319
    CrossrefPubMedSearch in Google Scholar
  • 42 Chanez P, Contin-Bordes C, Garcia G, Verkindre C, Didier A, Blay FD, Lara MTD, Blanco P, Moreau JF, Robinson P, Bourdeix I, Trunet P, Gros VL, Humbert M, Molimard M. Omalizumab-induced decrease of FcεRI expression in patients with severe allergic asthma. Respir Med 2010; 104: 1608-1617
    CrossrefPubMedSearch in Google Scholar