DOI QR코드

DOI QR Code

Efficacy of Herbal Medicines on Lung Function in Asthma: a systematic review and meta-analysis of randomized controlled trials

  • Alireza Derakhshan (Faculty of Traditional Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences) ;
  • Masoumeh Sadeghi (Department of Epidemiology, Faculty of Health, Mashhad University of Medical Sciences) ;
  • Amir-Mohammad-Hashem Asnaashari (Lung Disease Research Center, Faculty of Medicine, Mashhad University of Medical Sciences) ;
  • Mohsen Dehghani (Department of Epidemiology, School of Public Health, Iran University of Medical Sciences) ;
  • Roshanak Salari (Faculty of Traditional Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences) ;
  • Majid Khadem-Rezaiyan (Department of Community Medicine and Public Health, Faculty of Medicine, Mashhad University of Medical Sciences) ;
  • Majid Mirsadraee (Department of Internal Medicine, Faculty of Medicine, Islamic Azad University-Mashhad Branch) ;
  • Shahin Saeidinejat (Faculty of Traditional Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences) ;
  • Shima Jalali (Department of Internal, Mashhad University of Medical Sciences) ;
  • Shabnam Jalali (Department of Internal, Mashhad University of Medical Sciences)
  • Received : 2022.09.14
  • Accepted : 2023.02.17
  • Published : 2023.06.30

Abstract

Objectives: The present study was designed to conduct a comprehensive systematic review and meta-analysis to assess the efficacy of herbal medicines as add-on therapy on lung function in asthmatic patients. Methods: A comprehensive search of online databases was performed up to December 2021 to identify randomized controlled trials that used orally herbal preparations for asthma as add-on therapy. Studies were assessed for methodological quality using the Cochrane Collaboration's Risk of Bias tool. The main outcome was percent predicted value of forced expiratory volume (% predicted FEV1). Pooled weighted mean difference (WMD) estimate with corresponding 95% confidence interval (CI) was calculated using inversevariance weights method while random effects meta-analysis was used, taking into account clinical and conceptual heterogeneity. Results: As a result, 1,525 studies were identified. 169 studies were reviewed in-depth and 23 studies met our systematic review inclusion criteria. Finally, nine randomized controlled trials were included in the meta-analysis. Findings indicated that use of herbal medicines in patients with asthma significantly improved % predicted FEV1 (WMD: 3.73, 95% CI: 1.76-5.70), with no evidence for significant heterogeneity (p = 0.56 [Q statistic], I2 = 0.0%). In subgroup analysis by age, improvement in % predicted FEV1 was higher and significant in adults (WMD: 5.16; 95% CI: 2.68-7.63) compared to children (WMD = 1.27; 95% CI: -1.98-4.51). Sensitivity analysis showed the significant effect of herbal medicine consumption on improving FEV1 was consistently (range of summary WMDs: 3.27-4.59), indicating that the meta-analysis model was robust. There was no evidence of publication bias both visually and statistically. Conclusion: Findings support, the complementary use of herbal medicines resulted in significant improvement in the lung function compared to standard treatment in asthmatic patients with no considerable adverse events. This improvement is more likely to be observed amongst adults.

Keywords

Acknowledgement

The research was supported by the Vice-Chancellor for Research at the Mashhad University of Medical Sciences (MUMS) as part of a traditional Persian medical doctoral dissertation. Funding sources had no role in study design, data collection, analysis, interpretation, and manuscript preparation.

References

  1. Wang L, Cheng L, Yuan Q, Cui X, Shang H, Zhang B, et al. Adverse drug reactions of Shuanghuanglian injection: a systematic review of public literatures. J Evid Based Med. 2010;3(1):18-26.  https://doi.org/10.1111/j.1756-5391.2010.01067.x
  2. Rawat S, Jugran AK, Bhatt ID, Rawal RS. Hedychium spicatum: a systematic review on traditional uses, phytochemistry, pharmacology and future prospectus. J Pharm Pharmacol. 2018;70(6):687-712.  https://doi.org/10.1111/jphp.12890
  3. Pareek A, Suthar M, Rathore GS, Bansal V. Feverfew (Tanacetum parthenium L.): a systematic review. Pharmacogn Rev. 2011;5(9):103-10.  https://doi.org/10.4103/0973-7847.79105
  4. Babayigit A, Olmez D, Karaman O, Bagriyanik HA, Yilmaz O, Kivcak B, et al. Ginseng ameliorates chronic histopathologic changes in a murine model of asthma. Allergy Asthma Proc. 2008;29(5):493-8.  https://doi.org/10.2500/aap.2008.29.3137
  5. Yue GG, Chan BC, Kwok HF, To MH, Hon KL, Fung KP, et al. Screening for anti-inflammatory and bronchorelaxant activities of 12 commonly used Chinese herbal medicines. Phytother Res. 2012;26(6):915-25.  https://doi.org/10.1002/ptr.3659
  6. Hofmann D, Hecker M, Volp A. Efficacy of dry extract of ivy leaves in children with bronchial asthma--a review of randomized controlled trials. Phytomedicine. 2003;10(2-3):213-20.  https://doi.org/10.1078/094471103321659979
  7. Chan CK, Kuo ML, Shen JJ, See LC, Chang HH, Huang JL. Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial. Pediatr Allergy Immunol. 2006;17(5):316-22.  https://doi.org/10.1111/j.1399-3038.2006.00406.x
  8. Kim KI, Shin S, Lee N, Lee BJ, Lee J, Lee H. A traditional herbal medication, Maekmoondong-tang, for cough: a systematic review and meta-analysis. J Ethnopharmacol. 2016;178:144-54.  https://doi.org/10.1016/j.jep.2015.12.005
  9. Zhang Y, Qi D, Gao Y, Liang C, Zhang Y, Ma Z, et al. History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: a review. J Ethnopharmacol. 2020;260:112995. 
  10. Yang T, He J, Yan Y, Lian WW, Xia CY, Xu JK, et al. Euphorbia ebracteolata Hayata (Euphorbiaceae): a systematic review of its traditional uses, botany, phytochemistry, pharmacology, toxicology, and quality control. Phytochemistry. 2021;186:112736. 
  11. Yadav V, Krishnan A, Vohora D. A systematic review on Piper longum L.: bridging traditional knowledge and pharmacological evidence for future translational research. J Ethnopharmacol. 2020;247:112255. 
  12. Zhang C, Li J, Wu Z, Wang H, Que C, Zhao H, et al. Efficacy and safety of Anluohuaxian in the treatment of patients with severe Coronavirus disease 2019- a multicenter, open label, randomized controlled study: a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):495. 
  13. Hashempur MH, Mosavat SH, Heydari M, Shams M. Medicinal plants' use among patients with dyslipidemia: an Iranian cross-sectional survey. J Complement Integr Med. 2018;16(3):/j/jcim.2019. 
  14. Moghimi Sarani E, Ghorbannezhad F, Meshkibaf MH, Shakibaee M, Mosavat SH. Evaluation of the effect of alkaloid berberine on the positive and negative symptoms of the patients with schizophrenia: a double-blind randomized placebo-controlled clinical trial. Trad Integr Med. 2022;7(3):287-93.  https://doi.org/10.18502/tim.v7i3.10769
  15. Ou-Yang SH, Jiang T, Zhu L, Yi T. Dioscorea nipponica Makino: a systematic review on its ethnobotany, phytochemical and pharmacological profiles. Chem Cent J. 2018;12(1):57. 
  16. Namazi N, Larijani B, Ayati MH, Abdollahi M. The effects of Nigella sativa L. on obesity: a systematic review and meta-analysis. J Ethnopharmacol. 2018;219:173-81.  https://doi.org/10.1016/j.jep.2018.03.001
  17. Miraj S, Alesaeidi S, Kiani S. A systematic review of the relationship between dystemprament (sue Mizaj) and treatments and management of diseases (Ilaj and Eslah-e-Mizaj). Electron Physician. 2016;8(12):3378-84.  https://doi.org/10.19082/3378
  18. Ji T, Ji WW, Wang J, Chen HJ, Peng X, Cheng KJ, et al. A comprehensive review on traditional uses, chemical compositions, pharmacology properties and toxicology of Tetrastigma hemsleyanum. J Ethnopharmacol. 2021;264:113247. 
  19. He Y, Zhu L, Ma J, Wong L, Zhao Z, Ye Y, et al. Comprehensive investigation and risk study on pyrrolizidine alkaloid contamination in Chinese retail honey. Environ Pollut. 2020;267:115542. 
  20. Chen G, Chen Y, Chen Z, Gao S, Zhang P, Zhang H, et al. Sanao decoction for asthma: protocol of a systematic review. Medicine (Baltimore). 2019;98(18):e15313. 
  21. Jiang S, Cui H, Wu P, Liu Z, Zhao Z. Botany, traditional uses, phytochemistry, pharmacology and toxicology of Ilex pubescens Hook et Arn. J Ethnopharmacol. 2019;245:112147. 
  22. Chen Z, Zhang C, Gao F, Fu Q, Fu C, He Y, et al. A systematic review on the rhizome of Ligusticum chuanxiong Hort. (Chuanxiong). Food Chem Toxicol. 2018;119:309-325.  https://doi.org/10.1016/j.fct.2018.02.050
  23. Khorasanchi Z, Shafiee M, Kermanshahi F, Khazaei M, Ryzhikov M, Parizadeh MR, et al. Crocus sativus a natural food coloring and flavoring has potent anti-tumor properties. Phytomedicine. 2018;43:21-7.  https://doi.org/10.1016/j.phymed.2018.03.041
  24. Chen PY, Wang J, Lin YC, Li CC, Tsai CW, Liu TC, et al. 18-Carbon polyunsaturated fatty acids ameliorate palmitate-induced inflammation and insulin resistance in mouse C2C12 myotubes. J Nutr Biochem. 2015;26(5):521-31.  https://doi.org/10.1016/j.jnutbio.2014.12.007
  25. Huntley AL, Thompson Coon J, Ernst E. The safety of herbal medicinal products derived from Echinacea species: a systematic review. Drug Saf. 2005;28(5):387-400.  https://doi.org/10.2165/00002018-200528050-00003
  26. Wang Y, Chen S, Wang P, Tan C, Zhang C, Shi Z, et al. Comparison of clinical effectiveness of acupuncture and a Western drug on allergic rhinitis: study protocol for a randomized controlled trial. J Tradit Chin Med. 2014;34(3):254-60.  https://doi.org/10.1016/S0254-6272(14)60087-X
  27. Clark CE, Arnold E, Lasserson TJ, Wu T. Herbal interventions for chronic asthma in adults and children: a systematic review and meta-analysis. Prim Care Respir J. 2010 Dec;19(4):307-14.  https://doi.org/10.4104/pcrj.2010.00041
  28. Huntley A, Ernst E. Herbal medicines for asthma: a systematic review. Thorax. 2000;55(11):925-9.  https://doi.org/10.1136/thorax.55.11.925
  29. Arnold E, Clark CE, Lasserson TJ, Wu T. Herbal interventions for chronic asthma in adults and children. Cochrane Database Syst Rev. 200;(1):CD005989. 
  30. Ernst E. Frankincense: systematic review. BMJ. 2008;337:a2813. 
  31. Shergis JL, Wu L, Zhang AL, Guo X, Lu C, Xue CC. Herbal medicine for adults with asthma: a systematic review. J Asthma. 2016;53(6):650-9.  https://doi.org/10.3109/02770903.2015.1101473
  32. Singh BB, Khorsan R, Vinjamury SP, Der-Martirosian C, Kizhakkeveettil A, Anderson TM. Herbal treatments of asthma: a systematic review. J Asthma. 2007;44(9):685-98.  https://doi.org/10.1080/02770900701247202
  33. Chan PH, To CY, Chan EY, Li H, Zhang X, Chow PY, et al. A randomized placebo-controlled trial of traditional Chinese medicine as an add-on therapy to oral montelukast in the treatment of mild persistent asthma in children. Complement Ther Med. 2016;29:219-28.  https://doi.org/10.1016/j.ctim.2016.10.010
  34. Houssen ME, Ragab A, Mesbah A, El-Samanoudy AZ, Othman G, Moustafa AF, et al. Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma. Clin Biochem. 2010;43(10-11):887-90.  https://doi.org/10.1016/j.clinbiochem.2010.04.061
  35. Salem AM, Bamosa AO, Qutub HO, Gupta RK, Badar A, Elnour A, et al. Effect of Nigella sativa supplementation on lung function and inflammatory mediatorsin partly controlled asthma: a randomized controlled trial. Ann Saudi Med. 2017;37(1):64-71.  https://doi.org/10.5144/0256-4947.2017.64
  36. Urata Y, Yoshida S, Irie Y, Tanigawa T, Amayasu H, Nakabayashi M, et al. Treatment of asthma patients with herbal medicine TJ-96: a randomized controlled trial. Respir Med. 2002;96(6):469-74.  https://doi.org/10.1053/rmed.2002.1307
  37. Nejatbakhsh F, Karegar-Borzi H, Amin G, Eslaminejad A, Hosseini M, Bozorgi M, et al. Squill Oxymel, a traditional formulation from Drimia Maritima (L.) Stearn, as an add-on treatment in patients with moderate to severe persistent asthma: a pilot, triple-blind, randomized clinical trial. J Ethnopharmacol. 2017;196:186-92.  https://doi.org/10.1016/j.jep.2016.12.032
  38. Fleming PS, Koletsi D, Pandis N. Blinded by PRISMA: are systematic reviewers focusing on PRISMA and ignoring other guidelines? PLoS One. 2014;9(5):e96407. 
  39. Lin J, Yang D, Huang M, Zhang Y, Chen P, Cai S, et al. Chinese expert consensus on diagnosis and management of severe asthma. J Thorac Dis. 2018;10(12):7020-44.  https://doi.org/10.21037/jtd.2018.11.135
  40. Changizi Ashtiyani S, Shamsi M, Cyrus A, Bastani B, Tabata-bayei SM. A critical review of the works of pioneer physicians on kidney diseases in ancient Iran: Avicenna, Rhazes, Al-akhawayni, and Jorjani. Iran J Kidney Dis. 2011;5(5):300-8. 
  41. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane handbook for systematic reviews of interventions. Cochrane Database Syst Rev. 2019;10:ED000142. 
  42. Marin-Martinez F, Sanchez-Meca J. Weighting by inverse variance or by sample size in random-effects meta-analysis. Educ Psychol Meas. 2010;70(1):56-73.  https://doi.org/10.1177/0013164409344534
  43. Huedo-Medina TB, Sanchez-Meca J, Marin-Martinez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods. 2006;11(2):193-206.  https://doi.org/10.1037/1082-989X.11.2.193
  44. Somes GW. The generalized Mantel-Haenszel statistic. Am Stat. 1986;40(2):106-8.  https://doi.org/10.1080/00031305.1986.10475369
  45. Simmonds M. Quantifying the risk of error when interpreting funnel plots. Syst Rev. 2015;4:24. 
  46. Sterne JAC, Egger M. Regression methods to detect publication and other bias in meta-analysis. In: Rothstein HR, Sutton AJ, Borenstein M, editors. Publication bias in meta-analysis: prevention, assessment and adjustments. Chichester: John Wiley & Sons; 2005. p. 99-110. 
  47. Gjerdevik M, Heuch I. Improving the error rates of the Begg and Mazumdar test for publication bias in fixed effects meta-analysis. BMC Med Res Methodol. 2014;14:109. 
  48. Hosseini SA, Zilaee M, Shoushtari MH, Ghasemi Dehcheshmeh M. An evaluation of the effect of saffron supplementation on the antibody titer to heat-shock protein (HSP) 70, hsCRP and spirometry test in patients with mild and moderate persistent allergic asthma: a triple-blind, randomized placebo-controlled trial. Respir Med. 2018;145:28-34.  https://doi.org/10.1016/j.rmed.2018.10.016
  49. Wang X, Tian Z, Gao F, Zhang X, Liu J, Li Z. Traditional Chinese medicine as an adjunctive therapy to oral montelukast for treating patients with chronic asthma. Medicine (Baltimore). 2017; 96(51):e9291. 
  50. Chan PH, To CY, Chan EY, Li H, Zhang X, Chow PY, et al. A randomized placebo-controlled trial of traditional Chinese medicine as an add-on therapy to oral montelukast in the treatment of mild persistent asthma in children. Complement Ther Med. 2016;29:219-28.  https://doi.org/10.1016/j.ctim.2016.10.010
  51. Wong EL, Sung RY, Leung TF, Wong YO, Li AM, Cheung KL, et al. Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma. J Altern Complement Med. 2009;15(10):1091-7.  https://doi.org/10.1089/acm.2008.0626
  52. Hsu CH, Lu CM, Chang TT. Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma. Pediatr Allergy Immunol. 2005;16(1):76-81.  https://doi.org/10.1111/j.1399-3038.2005.00230.x
  53. Wen MC, Wei CH, Hu ZQ, Srivastava K, Ko J, Xi ST, et al. Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J Allergy Clin Immunol. 2005;116(3):517-24.  https://doi.org/10.1016/j.jaci.2005.05.029
  54. Chang TT, Huang CC, Hsu CH. Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment of allergic asthma. Phytother Res. 2006;20(5):342-7.  https://doi.org/10.1002/ptr.1843
  55. Murali PM, Rajasekaran S, Krishnarajasekar OR, Perumal T, Nalini K, Lakshmisubramanian S, et al. Plant-based formulation for bronchial asthma: a controlled clinical trial to compare its efficacy with oral salbutamol and theophylline. Respiration. 2006;73(4):457-63.  https://doi.org/10.1159/000089922
  56. Rouhi H, Ganji F, Nasri H. Effects of ginger on the improvement of asthma [The evaluation of its' treatmental effects]. Pak J Nutr. 2006;5(4):373-6.  https://doi.org/10.3923/pjn.2006.373.376
  57. Boskabady MH, Alizadeh M, Jahanbin B. Bronchodilatory effect of Carum copticum in airways of asthmatic patients. Therapie. 2007;62(1):23-9.  https://doi.org/10.2515/therapie:2007007
  58. Hoang BX, Shaw DG, Levine S, Hoang C, Pham P. New approach in asthma treatment using excitatory modulator. Phytother Res. 2007;21(6):554-7.  https://doi.org/10.1002/ptr.2107
  59. Thomas M, Sheran J, Smith N, Fonseca S, Lee AJ. AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study. BMC Pulm Med. 2007;7:4. 
  60. Watson RR, Zibadi S, Rafatpanah H, Jabbari F, Ghasemi R, Ghafari J, et al. Oral administration of the purple passion fruit peel extract reduces wheeze and cough and improves shortness of breath in adults with asthma. Nutr Res. 2008;28(3):166-71.  https://doi.org/10.1016/j.nutres.2008.01.003
  61. Kelly-Pieper K, Patil SP, Busse P, Yang N, Sampson H, Li XM, et al. Safety and tolerability of an antiasthma herbal Formula (ASHMI) in adult subjects with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation phase I study. J Altern Complement Med. 2009;15(7):735-43.  https://doi.org/10.1089/acm.2008.0543
  62. Park CS, Kim TB, Lee JY, Park JY, Lee YC, Jeong SS, et al. Effects of add-on therapy with NDC-052, an extract from Magnoliae Flos, in adult asthmatic patients receiving inhaled corticosteroids. Korean J Intern Med. 2012;27(1):84-90.  https://doi.org/10.3904/kjim.2012.27.1.84
  63. Smith LJ, Kalhan R, Wise RA, Sugar EA, Lima JJ, Irvin CG, et al.; American Lung Association Asthma Clinical Research Centers. Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial. JAMA. 2015;313:2033-43.  https://doi.org/10.1001/jama.2015.5024
  64. Kong L, Zhang H, Cao Y, Le J, Wu J, Liu B, et al. The anti-inflammatory effects of invigorating kidney and supplementing Qi Chinese herbal formulae in asthma patients. Evid Based Complement Alternat Med. 2017;2017:3754145. 
  65. Koshak A, Koshak E, Heinrich M. Medicinal benefits of Nigella sativa in bronchial asthma: a literature review. Saudi Pharm J. 2017;25(8):1130-6.  https://doi.org/10.1016/j.jsps.2017.07.002
  66. Power S, Williams M, Semprini A, Munro C, Caswell-Smith R, Pilcher J, et al. RCT of the effect of berryfruit polyphenolic cultivar extract in mild steroid-naive asthma: a cross-over, placebocontrolled study. BMJ Open. 2017;7(3):e013850. 
  67. Yugandhar P, Rao KM, Sengupta K. A novel herbal composition containing extracts of Boswellia serrata gum resin and Aegle marmelos fruit alleviates symptoms of asthma in a placebo controlled double-blind clinical study. Phytother Res. 2018;32(1):140-50.  https://doi.org/10.1002/ptr.5963
  68. Manarin G, Anderson D, Silva JME, Coppede JDS, Roxo-Junior P, Pereira AMS, et al. Curcuma longa L. ameliorates asthma control in children and adolescents: a randomized, double-blind, controlled trial. J Ethnopharmacol. 2019;238:111882. 
  69. Qasemzadeh MJ, Sharifi H, Hamedanian M, Gharehbeglou M, Heydari M, Sardari M, et al. The effect of Viola odorata flower syrup on the cough of children with asthma: a double-blind, randomized controlled trial. J Evid Based Complementary Altern Med. 2015;20(4):287-91.  https://doi.org/10.1177/2156587215584862
  70. Silva BM, Andrade PB, Ferreres F, Domingues AL, Seabra RM, Ferreira MA. Phenolic profile of quince fruit (Cydonia oblonga Miller) (pulp and peel). J Agric Food Chem. 2002;50(16):4615-8.  https://doi.org/10.1021/jf0203139
  71. Huang WY, Zhang HC, Liu WX, Li CY. Survey of antioxidant capacity and phenolic composition of blueberry, blackberry, and strawberry in Nanjing. J Zhejiang Univ Sci B. 2012;13(2):94-102.  https://doi.org/10.1631/jzus.B1100137
  72. Smruthi R, Divya M, Archana K, Ravi M. The active compounds of Passiflora spp and their potential medicinal uses from both in vitro and in vivo evidences. J Adv Biomed Pharm Sci. 2021;4(1):45-55. 
  73. Dong Y, Jia G, Hu J, Liu H, Wu T, Yang S, et al. Determination of alkaloids and flavonoids in Sophora flavescens by UHPLC-QTOF/MS. J Anal Methods Chem. 2021;2021:9915027. 
  74. Liu H, Lu X, Hu Y, Fan X. Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy. Pharmacol Res. 2020;161:105263. 
  75. Ghahari S, Alinezhad H, Nematzadeh GA, Tajbakhsh M, Baharfar R. Chemical composition, antioxidant and biological activities of the essential oil and extract of the seeds of Glycine max (Soybean) from North Iran. Curr Microbiol. 2017;74(4):522-31.  https://doi.org/10.1007/s00284-016-1188-4
  76. Sharma V, Katiyar A, Agrawal RC. Glycyrrhiza glabra: chemistry and pharmacological activity. In: Merillon JM, Ramawat K, editors. Sweeteners: Pharmacology, Biotechnology, and Applications. Cham: Springer; 2018. p. 87-100. 
  77. Topcagic A, Cavar Zeljkovic S, Karalija E, Galijasevic S, Sofic E. Evaluation of phenolic profile, enzyme inhibitory and antimicrobial activities of Nigella sativa L. seed extracts. Bosn J Basic Med Sci. 2017;17(4):286-94.  https://doi.org/10.17305/bjbms.2017.2049
  78. Mittal P, Gupta V, Goswami M, Thakur N, Bansal P. Phytochemical and pharmacological potential of Viola odorata. Int J Pharm. 2015;2(5):215-20. 
  79. Ude C, Schubert-Zsilavecz M, Wurglics M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet. 2013;52(9):727-49.  https://doi.org/10.1007/s40262-013-0074-5
  80. Huang HC. Sowing the seeds of health: is the era of food prescriptions coming? J Chin Med Assoc. 2014;77(6):273-4.  https://doi.org/10.1016/j.jcma.2014.04.001
  81. Chen L, Mehrabi Nasab E, Athari SS. Effect of loaded glycyrrhizic acid on PLGA nano-particle on treatment of allergic asthma. Iran J Allergy Asthma Immunol. 2022;21(1):65-72.  https://doi.org/10.18502/ijaai.v21i1.8617
  82. Derakhshan AR. Natural treatments for fissure in Ano used by traditional Persian scholars, Razi (Rhazes) and Ibn Sina (Avicenna). J Evid Based Complementary Altern Med. 2017;22(2):324-33.  https://doi.org/10.1177/2156587216650302
  83. Ghasemzadeh A, Jaafar HZ, Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules. 2010;15(6):4324-33. https://doi.org/10.3390/molecules15064324