Home Hydro-alcoholic extract of Morus nigra reduces fasting blood glucose and HbA1c% in diabetic patients, probably via competitive and allosteric interaction with alpha-glucosidase enzyme; a clinical trial and in silico analysis
Article
Licensed
Unlicensed Requires Authentication

Hydro-alcoholic extract of Morus nigra reduces fasting blood glucose and HbA1c% in diabetic patients, probably via competitive and allosteric interaction with alpha-glucosidase enzyme; a clinical trial and in silico analysis

  • Hamid Momeni , Ashraf Salehi , Abdorrahim Absalan and Mehran Akbari EMAIL logo
Published/Copyright: May 5, 2021
Journal of Complementary and Integrative Medicine
From the journal Journal of Complementary and Integrative Medicine Volume 19 Issue 3

Abstract

Objectives

1-Deoxynojirimycin (1-DNJ), the main active component found in Morus nigra (black mulberry) is reported to be effective in controlling diabetes. We have evaluated the effect of hydro-alcoholic extract of M. nigra leaves on the fasting blood glucose (FBS) and hemoglobin A1c% (HbA1c%) in diabetic patients. Furthermore, we compared the interaction of 1-DNJ and glucose molecules with the alpha-glucosidase enzyme, which has a critical role in the lysis of glucose-based polymers in human cells.

Methods

4% hydro-alcoholic extract was prepared from black mulberry leaves. Patients in treatment (n=50) and control (n=50) groups received 3 mL extract or placebo in water, respectively, and three times a day. Fasting blood glucose and HbA1c% were evaluated before and after three months of evaluation. Potential binding sites of 1-DNJ or glucose on the enzyme glucosidase found by docking study. Docking scores were obtained using an energy minimization method by Molegro Virtual Docker software. The Mean ± SD of each variable was compared between groups at the 95% significant level.

Results

Age mean ± SD was equal to 54.79 ± 9.203 (38–69) years. There was no significant difference between intervention and placebo groups considering FBS (p=0.633) but was for HbA1c% (p=0.0011), before treatment. After three months, both FBS and HbA1c% were significantly reduced in patients under mulberry leaves extract-treatment. FBS changed was from 182.23 ± 38.65 to 161.23 ± 22.14 mg/dL in treatment group (p<0.001) and from 178.45 ± 39.46 to 166.23 ± 29.64 mg/dL in control group (p<0.001). HbA1c was changed from 7.23 ± 0.25 to 6.13 ± 0.61% in treatment group (p<0.001) and from 7.65 ± 0.85 to 7.12 ± 0.33% in control group (p=0.854). Docking results showed that 1-DNJ binds more efficiently, and with a significant score than glucose, to human alpha-glucosidase.

Conclusions

This clinical trial and virtual analysis showed that a hydro-alcoholic extract of black mulberry (M. nigra) leaf may be efficient in reducing the blood glucose and HbA1c% in diabetic patients. Furthermore, docking studies propose a competitive and allosteric regulation for herbal ingredients. Drug-development could be based on the presented idea in this report.

Keywords: diabetes; glucosidase; hemoglobin A1c; Morus nigra ; virtual analysis
Corresponding author: Mehran Akbari, Department of Nursing, Khomein University of Medical Sciences, Khomein, Iran, Mobile: +989373471255, E-mail:

Funding source: Arak University of Medical Sciences

Award Identifier / Grant number: 1214

Acknowledgments

The presented study is evaluated and accepted by the research office of Arak University of medical sciences. Therefore, the authors declare the best regards and thanks to dear coworkers in the mentioned department. Furthermore, we thank all dear patients who were included in the study and permit us to do the current work.

  1. Research funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Arak University of Medical Sciences, Arak, Iran (No: 1214).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Conflict of interest: The authors declare that there is no conflict of interest for publishing the paper in its current format.

  4. Ethical approval: The Ethics Committee of Arak University of Medical Sciences, Arak, Iran, approved this study (93-170-2).

References

1. Wild, S, Roglic, G, Green, A, Sicree, R, King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–53. https://doi.org/10.2337/diacare.27.5.1047.Search in Google Scholar PubMed

2. Esteghamati, A, Gouya, MM, Abbasi, M, Delavari, A, Alikhani, S, Alaedini, F, et al.. Prevalence of diabetes and impaired fasting glucose in the adult population of Iran: National Survey of risk factors for non-communicable diseases of Iran. Diabetes Care 2008;31:96–8. https://doi.org/10.2337/dc07-0959.Search in Google Scholar PubMed

3. King, H. WHO and the International diabetes Federation: regional partners. Bull World Health Organ 1999;77:954.Search in Google Scholar

4. Henry, CJ, Kaur, B, Quek, RYC. Chrononutrition in the management of diabetes. Nutr Diabetes 2020;10:1–11. https://doi.org/10.1038/s41387-020-0109-6.Search in Google Scholar PubMed PubMed Central

5. Heisler, M, Smith, DM, Hayward, RA, Krein, SL, Kerr, EA. How well do patients’ assessments of their diabetes self-management correlate with actual glycemic control and receipt of recommended diabetes services? Diabetes Care 2003;26:738–43. https://doi.org/10.2337/diacare.26.3.738.Search in Google Scholar PubMed

6. Rubin, RR, Peyrot, M, Saudek, CD. Differential effect of diabetes education on self-regulation and life-style behaviors. Diabetes Care 1991;14:335–7. https://doi.org/10.2337/diacare.14.4.335.Search in Google Scholar PubMed

7. Beyene, B, Beyene, B, Deribe, H. Review on application and management of medicinal plants for the livelihood of the local community. J Resour Dev Manag 2016;22:33–9.Search in Google Scholar

8. Razzaque, M, Talukder, N, Islam, M, Bhadra, A, Dutta, R. The effect of salinity on morphological characteristics of seven rice (Oryza sativa) genotypes differing in salt tolerance. Pak J Biol Sci: PJBS 2009;12:406–12. https://doi.org/10.3923/pjbs.2009.406.412.Search in Google Scholar PubMed

9. Gruenwald, J, Freder, J, Armbruester, N. Cinnamon and health. Crit Rev Food Sci Nutr 2010;50:822–34. https://doi.org/10.1080/10408390902773052.Search in Google Scholar PubMed

10. Khan, A, Safdar, M, Khan, MMA, Khattak, KN, Anderson, RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215–8. https://doi.org/10.2337/diacare.26.12.3215.Search in Google Scholar PubMed

11. Hasani-Ranjbar, S, Larijani, B, Abdollahi, M. A systematic review of Iranian medicinal plants useful in diabetes mellitus. Arch Med Sci 2008;4:285–92.Search in Google Scholar

12. Anderson, RA. Chromium and polyphenols from cinnamon improve insulin sensitivity: plenary lecture. Proc Nutr Soc 2008;67:48–53. https://doi.org/10.1017/s0029665108006010.Search in Google Scholar

13. Andallu, B, Varadacharyulu, N. Gluconeogenic substrates and hepatic gluconeogenic enzymes in streptozotocin-diabetic rats: effect of mulberry (Morus indica L.) leaves. J Med Food 2007;10:41–8. https://doi.org/10.1089/jmf.2005.034.Search in Google Scholar PubMed

14. Liu, H-Y, Fang, M, Zhang, Y-Q. In vivo hypoglycaemic effect and inhibitory mechanism of the branch bark extract of the mulberry on STZ-induced diabetic mice. Sci World J 2014;2014. https://doi.org/10.1155/2014/614265.Search in Google Scholar

15. Rashidi, AA, Mirhashemi, SM, Taghizadeh, M, Sarkhail, P. Iranian medicinal plants for diabetes mellitus: a systematic review. Pak J Biol Sci: PJBS. 2013;16:401–11. https://doi.org/10.3923/pjbs.2013.401.411.Search in Google Scholar

16. Wu, H, Zeng, W, Chen, L, Yu, B, Guo, Y, Chen, G, et al.. Integrated multi-spectroscopic and molecular docking techniques to probe the interaction mechanism between maltase and 1-deoxynojirimycin, an α-glucosidase inhibitor. Int J Biol Macromol 2018;114:1194–202. https://doi.org/10.1016/j.ijbiomac.2018.04.024.Search in Google Scholar

17. Coutinho, PM, Dowd, MK, Reilly, PJ. Automated docking of monosaccharide substrates and analogues and methyl α‐acarviosinide in the glucoamylase active site. Proteins: Struct Funct Bioinform 1997;27:235–48. https://doi.org/10.1002/(sici)1097-0134(199702)27:2<235::aid-prot10>3.0.co;2-n.10.1002/(SICI)1097-0134(199702)27:2<235::AID-PROT10>3.0.CO;2-NSearch in Google Scholar

18. Karthik, L, Malathy, P, Trinitta, A, Gunasekaran, K. Molecular docking with Trehalose-6 phosphate phosphatase: a potential drug target of Filaral parasite ‘Brugia malayi’. Lett Drug Des Discov 2011;8:363–70. https://doi.org/10.2174/157018011794839402.Search in Google Scholar

19. Absalan, A, Mesbah-Namin, SA, Tiraihi, T, Taheri, T. Cinnamaldehyde and eugenol change the expression folds of AKT1 and DKC1 genes and decrease the telomere length of human adipose-derived stem cells (hASCs): an experimental and in silico study. Iran J Basic Med Sci 2017;20:316. https://doi.org/10.22038/ijbms.2017.8362.Search in Google Scholar

20. Parsaeyan, NM-KH, Absalan, A, Mozayan, MR. Beneficial effects of cocoa on lipid peroxidation and inflammatory markers in type 2 diabetic patients and investigation of probable interactions of cocoa active ingredients with prostaglandin synthase-2 (PTGS-2/COX-2) using virtual analysis. J Diabetes Metab Disord 2014;13:30. https://doi.org/10.1186/2251-6581-13-30.Search in Google Scholar

21. Irwin, JJ, Sterling, T, Mysinger, MM, Bolstad, ES, Coleman, RG. ZINC: a free tool to discover chemistry for biology. J Chem Inf Model 2012;52:1757–68. https://doi.org/10.1021/ci3001277.Search in Google Scholar

22. Yazdanpanah, L, Shahbazian, H, Aleali, AM, Jahanshahi, A, Ghanbari, S, Latifi, S. Prevalence, awareness and risk factors of diabetes in Ahvaz (South West of Iran). Diabetes Metab Syndr 2016;10:S114–8. https://doi.org/10.1016/j.dsx.2016.03.007.Search in Google Scholar

23. Mirzaei, M, Khajeh, M, Askarishahi, M, Azizi, R. Behavioral and familial predictors of diabetes mellitus in adults aged 20–69 in Yazd, Iran during 2014–2015. Clin Res Rev 2018;12:667–71. https://doi.org/10.1016/j.dsx.2018.04.002.Search in Google Scholar PubMed

24. Mirzaei, M, Khajeh, M. Comparison of anthropometric indices (body mass index, waist circumference, waist to hip ratio and waist to height ratio) in predicting risk of type II diabetes in the population of Yazd, Iran. Clin Res Rev 2018;12:677–82. https://doi.org/10.1016/j.dsx.2018.04.026.Search in Google Scholar PubMed

25. Eva, JJ, Kassab, YW, Neoh, CF, Ming, LC, Wong, YY, Abdul Hameed, M, et al.. Self-care and self-management among adolescent T2DM patients: a review. Front Endocrinol 2018;9:489. https://doi.org/10.3389/fendo.2018.00489.Search in Google Scholar PubMed PubMed Central

26. Falcón, SC, Guedes, BV, Alvarado-Martel, D, Wägner, AM. Preconception care in diabetes: predisposing factors and barriers. Endocrinol Diabetes Nutr (English ed) 2018;65:164–71.10.1016/j.endien.2017.10.015Search in Google Scholar

27. Lo, S-F, Chen, W-L, Muo, C-H, Chen, P-C, Chen, S-Y, Kuo, CL, et al.. Microvascular parameters help to predict stroke risk in the Asian diabetic population in Taiwan: a population based case-control study. Front Neurol 2018;9:719. https://doi.org/10.3389/fneur.2018.00719.Search in Google Scholar PubMed PubMed Central

28. Benoit, SR, Fleming, R, Philis-Tsimikas, A, Ji, M. Predictors of glycemic control among patients with Type 2 diabetes: a longitudinal study. BMC Publ Health 2005;5:1–9. https://doi.org/10.1186/1471-2458-5-36.Search in Google Scholar PubMed PubMed Central

29. Association, AD. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2019. Diabetes Care 2019;42(1 Suppl):S13–28.10.2337/dc19-S002Search in Google Scholar PubMed

30. Agrawal, R, Sharma, A, Dua, A, Kochar, D, Kothari, R. A randomized placebo controlled trial of Inolter (herbal product) in the treatment of type 2 diabetes. J Assoc Phys India 2002;50:391–3.Search in Google Scholar

31. Deng, R. A review of the hypoglycemic effects of five commonly used herbal food supplements. Recent patents on food. Nutr Agric 2012;4:50–60. https://doi.org/10.2174/1876142911204010050.Search in Google Scholar

32. Blevins, SM, Leyva, MJ, Brown, J, Wright, J, Scofield, RH, Aston, CE. Effect of cinnamon on glucose and lipid levels in non-insulin-dependent type 2 diabetes. Diabetes Care 2007;30:2236–7. https://doi.org/10.2337/dc07-0098.Search in Google Scholar PubMed

33. Mang, B, Wolters, M, Schmitt, B, Kelb, K, Lichtinghagen, R, Stichtenoth, D, et al.. Effects of a cinnamon extract on plasma glucose, HbA1c, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest 2006;36:340–4. https://doi.org/10.1111/j.1365-2362.2006.01629.x.Search in Google Scholar PubMed

34. Naowaboot, J, Pannangpetch, P, Kukongviriyapan, V, Prawan, A, Kukongviriyapan, U, Itharat, A. Mulberry leaf extract stimulates glucose uptake and GLUT4 translocation in rat adipocytes. Am J Chin Med 2012;40:163–75. https://doi.org/10.1142/s0192415x12500139.Search in Google Scholar

35. Naowaboot, J, Pannangpetch, P, Kukongviriyapan, V, Kongyingyoes, B. Antihyperglycemic, antioxidant and antiglycation activities of mulberry leaf extract in streptozotocin-induced chronic diabetic rats. Plant Foods Hum Nutr 2009;64:116–21. https://doi.org/10.1007/s11130-009-0112-5.Search in Google Scholar PubMed

36. Mohammadi, J, Naik, PR. Evaluation of hypoglycemic effect of Morus alba in an animal model. Indian J Pharmacol 2008;40:15. https://doi.org/10.4103/0253-7613.40483.Search in Google Scholar PubMed PubMed Central

37. Nakagawa, K, Kubota, H, Kimura, T, Yamashita, S, Tsuzuki, T, Oikawa, S, et al.. Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma. J Agric Food Chem 2007;55:8928–33. https://doi.org/10.1021/jf071559m.Search in Google Scholar PubMed

38. Hansawasdi, CKJ. Alpha-glucosidase inhibitory effect of mulberry (Morus alba) leaves on Caco-2. Fitoterapia 2006;77:568–73. https://doi.org/10.1016/j.fitote.2006.09.003.Search in Google Scholar PubMed

39. Liu, Q, Li, X, Li, C, Zheng, Y, Peng, G. 1-Deoxynojirimycin alleviates insulin resistance via activation of insulin signaling PI3K/AKT pathway in skeletal muscle of db/db mice. Molecules 2015;20:21700–14. https://doi.org/10.3390/molecules201219794.Search in Google Scholar PubMed PubMed Central

40. Yuan, A-H, Ma, J, Jiang, X-F, Li, S. Screening of glucosidase inhibitors from various fractions of mulberry leaves. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi= China J Chin Mat Med 2006;31:223–7.Search in Google Scholar

41. Kumar, D, Bajaj, S, Mehrotra, R. Knowledge, attitude and practice of complementary and alternative medicines for diabetes. Publ Health 2006;120:705–11. https://doi.org/10.1016/j.puhe.2006.04.010.Search in Google Scholar PubMed

42. Hays, NP, Galassetti, PR, Coker, RH. Prevention and treatment of type 2 diabetes: current role of lifestyle, natural product, and pharmacological interventions. Pharmacol Ther 2008;118:181–91. https://doi.org/10.1016/j.pharmthera.2008.02.003.Search in Google Scholar PubMed PubMed Central

43. Hanhineva, K, Törrönen, R, Bondia-Pons, I, Pekkinen, J, Kolehmainen, M, Mykkänen, H, et al.. Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci 2010;11:1365–402. https://doi.org/10.3390/ijms11041365.Search in Google Scholar PubMed PubMed Central

44. Mandal, S, Mandal, SK. Rational drug design. Eur J Pharmacol 2009;625:90–100. https://doi.org/10.1016/j.ejphar.2009.06.065.Search in Google Scholar PubMed

45. Tao, G, Irie, Y, Li, D-J, Keung, WM. Eugenol and its structural analogs inhibit monoamine oxidase A and exhibit antidepressant-like activity. Bioorg Med Chem 2005;13:4777–88. https://doi.org/10.1016/j.bmc.2005.04.081.Search in Google Scholar PubMed

46. Absalan, A, Mohiti-Ardakani, J, Hadinedoushan, H, Khalili, MA. Hydro-alcoholic cinnamon extract, enhances glucose transporter isotype-4 translocation from intracellular compartments into the cytoplasmic membrane of C2C12 myotubes. Indian J Clin Biochem 2012;27:351–6. https://doi.org/10.1007/s12291-012-0214-y.Search in Google Scholar PubMed PubMed Central

Received: 2021-01-04
Accepted: 2021-02-07
Published Online: 2021-05-05

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Evidence implementation among complementary medicine practitioners: a meta-summary
  4. Phytochemical: a treatment option for heavy metal induced neurotoxicity
  5. The effects of curcumin-containing supplementations on inflammatory markers and lipid profiles in patients with chronic kidney diseases: a systematic review and meta-analysis of randomized controlled trials
  6. A systematic review on traditional medicinal Animal’s parts and products used for the treatment of respiratory tract disorders in Ethiopia
  7. Review on nutraceuticals: phase transition from preventive to protective care
  8. A study of effect of Centella asiatica on oxidative markers in the hippocampus of offsprings born to alcohol-fed pregnant rats and the correlation with their cognitive functions
  9. Anxiogenic and anxiolytic effects of memantine injected into the ventral hippocampus in male stressed mice
  10. Research Articles
  11. Comparison of antithyroid effects and hepatic complications of methimazole with catechin and its nanoencapsulation form in adult male rats
  12. Almond oil restores blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism
  13. Highly efficient microencapsulation of phytonutrients by fractioned cellulose using biopolymer complexation technology
  14. Ocimum basilicum alleviates blood glucose, lipid profile and iNOS in diabetes gestational rat model
  15. Blood pressure and blood sugar-lowering effects of purified gambir on diabetic hypertensive Wistar Kyoto rats
  16. Assessment of anti-inflammatory and antioxidant activity of quercetin–rutin blend (SophorOx™) – an invitro cell based assay
  17. Subchronic toxicological evaluation of EnXtra™ (standardised extract of Alpinia galanga rhizome) in rats
  18. Ficus glumosa Del. reduces phenylhydrazine-induced hemolytic anaemia and hepatic damage in Wistar rats
  19. Screening of anti-cancerous potential of classical Raudra rasa and modified Raudra rasa modified with hiraka bhasma (nanodiamond) through FTIR & LC-MS analysis
  20. Aqueous extract of Pedalium murex D. Royen ex L. leafy stem protects against lead induced testicular toxicity in Wistar rats
  21. Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze
  22. Developmental effects of early-life stress on dopamine D2 receptor and proteins involved in noncanonical D2 dopamine receptor signaling pathway in the prefrontal cortex of male rats
  23. Probiotic administration enhanced antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei
  24. Acacia arabica (Lam.) Willd. On osteoblastogenesis, osteoblast proliferation, osteoclastic activity, and bone calcium mineralization
  25. GC-MS analysis of curculigo orchiodes and medicinal herbs with cytotoxic, hepatoprotective attributes of ethanolic extract from Indian origin
  26. Biochemical and histopathological evaluation of liver, kidney, and pancreas in normal Sprague Dawley rats administered aqueous extract of beetroot (Beta vulgaris)
  27. The effectiveness of emotional freedom techniques (EFT) on depression of postmenopausal women: a randomized controlled trial
  28. The formulation and efficacy of topical Dorema ammoniacum in treating Melasma: a randomized double-blind, placebo-controlled trial
  29. Impact of inhalation aromatherapy with Damask Rose (Rosa damascena) on stress, anxiety and hemodynamic parameters of patients undergoing coronary angiography: a single blind randomized clinical trial
  30. Hydro-alcoholic extract of Morus nigra reduces fasting blood glucose and HbA1c% in diabetic patients, probably via competitive and allosteric interaction with alpha-glucosidase enzyme; a clinical trial and in silico analysis
  31. Prophylactic management of radiation-induced mucositis using herbal mouthwash in patients with head and neck cancer: an assessor-blinded randomized controlled trial
  32. Implementation science in New Zealand naturopathic practice: a cross-sectional study
  33. Issues of mindfulness implementation for oncology caregivers
  34. Immediate effect of cold mud pack therapy on autonomic variables in primary hypertensive individuals: a randomized trial
  35. Effect of a Persian metabolic diet on the functional dyspepsia symptoms in patients with postprandial distress syndrome: a randomized, double-blind clinical trial
https://doi.org/10.1515/jcim-2021-0005
Keywords for this article
diabetes; glucosidase; hemoglobin A1c; Morus nigra; virtual analysis

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Evidence implementation among complementary medicine practitioners: a meta-summary
  4. Phytochemical: a treatment option for heavy metal induced neurotoxicity
  5. The effects of curcumin-containing supplementations on inflammatory markers and lipid profiles in patients with chronic kidney diseases: a systematic review and meta-analysis of randomized controlled trials
  6. A systematic review on traditional medicinal Animal’s parts and products used for the treatment of respiratory tract disorders in Ethiopia
  7. Review on nutraceuticals: phase transition from preventive to protective care
  8. A study of effect of Centella asiatica on oxidative markers in the hippocampus of offsprings born to alcohol-fed pregnant rats and the correlation with their cognitive functions
  9. Anxiogenic and anxiolytic effects of memantine injected into the ventral hippocampus in male stressed mice
  10. Research Articles
  11. Comparison of antithyroid effects and hepatic complications of methimazole with catechin and its nanoencapsulation form in adult male rats
  12. Almond oil restores blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism
  13. Highly efficient microencapsulation of phytonutrients by fractioned cellulose using biopolymer complexation technology
  14. Ocimum basilicum alleviates blood glucose, lipid profile and iNOS in diabetes gestational rat model
  15. Blood pressure and blood sugar-lowering effects of purified gambir on diabetic hypertensive Wistar Kyoto rats
  16. Assessment of anti-inflammatory and antioxidant activity of quercetin–rutin blend (SophorOx™) – an invitro cell based assay
  17. Subchronic toxicological evaluation of EnXtra™ (standardised extract of Alpinia galanga rhizome) in rats
  18. Ficus glumosa Del. reduces phenylhydrazine-induced hemolytic anaemia and hepatic damage in Wistar rats
  19. Screening of anti-cancerous potential of classical Raudra rasa and modified Raudra rasa modified with hiraka bhasma (nanodiamond) through FTIR & LC-MS analysis
  20. Aqueous extract of Pedalium murex D. Royen ex L. leafy stem protects against lead induced testicular toxicity in Wistar rats
  21. Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze
  22. Developmental effects of early-life stress on dopamine D2 receptor and proteins involved in noncanonical D2 dopamine receptor signaling pathway in the prefrontal cortex of male rats
  23. Probiotic administration enhanced antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei
  24. Acacia arabica (Lam.) Willd. On osteoblastogenesis, osteoblast proliferation, osteoclastic activity, and bone calcium mineralization
  25. GC-MS analysis of curculigo orchiodes and medicinal herbs with cytotoxic, hepatoprotective attributes of ethanolic extract from Indian origin
  26. Biochemical and histopathological evaluation of liver, kidney, and pancreas in normal Sprague Dawley rats administered aqueous extract of beetroot (Beta vulgaris)
  27. The effectiveness of emotional freedom techniques (EFT) on depression of postmenopausal women: a randomized controlled trial
  28. The formulation and efficacy of topical Dorema ammoniacum in treating Melasma: a randomized double-blind, placebo-controlled trial
  29. Impact of inhalation aromatherapy with Damask Rose (Rosa damascena) on stress, anxiety and hemodynamic parameters of patients undergoing coronary angiography: a single blind randomized clinical trial
  30. Hydro-alcoholic extract of Morus nigra reduces fasting blood glucose and HbA1c% in diabetic patients, probably via competitive and allosteric interaction with alpha-glucosidase enzyme; a clinical trial and in silico analysis
  31. Prophylactic management of radiation-induced mucositis using herbal mouthwash in patients with head and neck cancer: an assessor-blinded randomized controlled trial
  32. Implementation science in New Zealand naturopathic practice: a cross-sectional study
  33. Issues of mindfulness implementation for oncology caregivers
  34. Immediate effect of cold mud pack therapy on autonomic variables in primary hypertensive individuals: a randomized trial
  35. Effect of a Persian metabolic diet on the functional dyspepsia symptoms in patients with postprandial distress syndrome: a randomized, double-blind clinical trial
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 11.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jcim-2021-0005/html
Scroll to top button