The Effects of Shilajit on Brain Edema

By: 1 Mohammad Khaksari; 2 Reza Mahmmodi; 3 Nader Shah

The Effects of Shilajit on Brain Edema, Intracranial Pressure and Neurologic Outcomes following the Traumatic Brain Injury in Rat

Article 8Volume 16, Issue 7, July 2013, Page 858-864  

Document Type: Original Article


1 Mohammad Khaksari2 Reza Mahmmodi3 Nader Shahrokhi* 3 Mohammad Shabani1 Siavash Joukar4 Mobin Aqapour

1Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

2Jiroft Education, Jiroft, Iran

3Neuroscience Research Center ,Kerman University of Medical Sciences, Kerman, Iran

4Mobin kahroba kimia Company, Kerman, Iran



Brain edema is one of the most serious causes of death within the first few days after trauma brain injury (TBI). In this study we have investigated the role of Shilajit on brain edema, blood-brain barrier (BBB) permeability, intracranial pressure (ICP) and neurologic outcomes following brain trauma. 
Materials and Methods: 
Diffuse traumatic brain trauma was induced in rats by drop of a 250 g weight from a 2 m high (Marmarou’s methods). Animals were randomly divided into 5 groups including sham, TBI, TBI-vehicle, TBI-Shi150 group and TBI-Shi250 group. Rats were undergone intraperitoneal injection of Shilajit and vehicle at 1, 24, 48 and 72 hr after trauma. Brain water content, BBB permeability, ICP and neurologic outcomes were finally measured. 
Brain water and Evans blue dye contents showed significant decrease in Shilajit-treated groups compared to the TBI-vehicle and TBI groups. Intracranial pressure at 24, 48 and 72 hr after trauma had significant reduction in Shilajit-treated groups as compared to TBI-vehicle and TBI groups (P<0.001). The rate of neurologic outcomes improvement at 4, 24, 48 and 72 hr after trauma showed significant increase in Shilajit-treated groups in comparison to theTBI- vehicle and TBI groups (P <0.001). 
The present results indicated that Shilajit may cause in improvement of neurologic outcomes through decreasing brain edema, disrupting of BBB, and ICP after the TBI.


Brain edema Intracranial pressure Rat Shilajit Trauma


1. Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil 2006; 21:544-548.

2. Andelic N, Sigurdardottir S, Brunborg C, Roe C. Incidence of hospital-treated traumatic brain injury in the Oslo population. Neuroepidemiology 2008; 30(2):120-8.

3. Education MoHaM. Development and Coordination of Statistical Yearbook of mortality in 2000. Tehran: Ministry of Health and Medical Education; 2001.

4. Yin H, Yang EJ, Park SJ, Han SK. Glycine- and GABA-mimetic Actions of shilajit on the substantia gelatinosa neurons of the trigeminal subnucleus cudalis in mice. Korean J Physiol Pharmacol 2011; 15:285-289.

5. Jayakumar AR, Rao KV, Panickar KS, Moriyama M, Reddy PV, Norenberg MD. Trauma-induced cell swelling in cultured astrocytes. J Neuropathol Exp Neurol 2008; 67:417-427.

6. Lu J, Goh SJ, Tng PY, Deng YY, Ling EA, Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Front Biosci 2009; 14:3795-3813.

7. Roberts I, Schierhout G, Alderson P. Absence of evidence for the effectiveness of five interventions routinely used in the intensive care management of severe head injury: a systematic review. J Neurol Neurosurg Psychiatry 1998; 65:729-733.

Shilajit and Traumatic Brain Injury Khaksari et al

Iran J Basic Med Sci, Vol. 16, No. 7, Jul 2013



8. Wang KK, Larner SF, Robinson G, Hayes RL. Neuroprotection targets after traumatic brain injury. Curr Opin Neurol 2006; 19:514-519.

9. Shibnath Ghosal SKS, Yatendra Kumar, Radheyshyam Srivastava, Raj K. Goel, Radharaman Dey, Salil K. Bhattacharya. Anti-ulcerogenic activity of fulvic acids and 4′-methoxy-6-carbomethoxybiphenyl isolated from shilajit. Phytotherapy Research 1988;2(4):187-91.

10. Goel RK, Banerjee RS, Acharya SB. Antiulcerogenic and antiinflammatory studies with shilajit. J Ethnopharmacol 1990; 29:95-103.

11. ASh S. [Effect of "Mumie" on Bone Regeneration and Blood Alkaline Phosphatase in Experimental Fractures of the Tubular Bones]. Ortop Travmatol Protez. 1965 May;26:24-7.

12. Kel'ginbaev NS, Sorokina VA, Stefanidu AG, Ismailova VN. [Treatment of long tubular bone fractures with Mumie Assil preparations in experiments and clinical conditions]. Eksp Khir Anesteziol 1973-; 18:31-35.

13. Mohd. Aamir Mirza MNA, Mohd. Faiyazuddin,, Danish Mahmood RBaGM. Shilajit: An Ancient Panacea. Int J Curr Pharmaceut Rev Res 2010; 1:2-11.

14. Assegid Garedewa MF, Erik Schmolza, Ingolf Lamprecht. Thermal analysis of mumiyo, the legendary folkremedy from the Himalaya region. Thermochimica Acta. 2004; 417( 2):301-9.

15. Aiello A, Fattorusso E, Menna M, Vitalone R, Schrِder HC, Müller WE. Mumijo traditional medicine: fossil deposits from antarctica (chemical composition and beneficial bioactivity). Evid Based Complement Alternat Med 2008; 2011:1-8.

16. Ghosal S LJ, Jaiswal AK, Bhattacharya SK. Effects of Shilajit and its active constituents on learning and memory in rats. Phytother Res 1993a; 7:29 -34.

17. Spassov V. Memory effects of the natural product Mumyo on the water maze in rats. Eur Neuropsychopharmacol 1994; 4:396.

18. Bhattacharya SKaS, A. P. Effects of Shilajit on biogenic free radicals. Phytother Res 1995; 9 56-59.

19. Agarwal SP, Khanna R, Karmarkar R, Anwer MK, Khar RK. Shilajit: A Review. Phytother Res 2007; 21:401-405.

20. Effect of Shilajit on rat brain monoamines. Phytother Res 1992; 6:163-164.

21. Thawatchai Phaechamud JC, Wetwitayaklung P, Chutima Limmatvapirat and Thaksin Srichan. Some Biological Activities and Safety of Mineral Pitch(Mumijo). Silpakorn U Sience & Tech J 2008; 2:7-17.

22. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 1994; 80:291-300.

23. keshavarzi ZMK, Razmi Z, Soltani Hekmat A, Naderi V, Rostami S. The effects of cyclooxygenase inhibitors on the brain Iiflammatory response following traumatic brain injury in rats. Iran J Basic Med Sci 2012; 15:1102-1105.

24. Khaksari M, Soltani Z, Shahrokhi N, Moshtaghi G, Asadikaram G. The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury. Can J Physiol Pharmacol 2010; 89:31-40.

25. Shahrokhi N, Khaksari M, Soltani Z, Mahmoodi M, Nakhaee N. Effect of sex steroid hormones on brain edema, intracranial pressure, and neurologic outcomes after traumatic brain injury. Can J Physiol Pharmacol 2010; 88:414-421.

26. O'Connor CA, Cernak I, Vink R. Both estrogen and progesterone attenuate edema formation following diffuse traumatic brain injury in rats. Brain Res 2005; 1062:171-174.

27. Pegg CC, He C, Stroink AR, Kattner KA, Wang CX. Technique for collection of cerebrospinal fluid from the cisterna magna in rat. J Neurosci Methods 2010; 187:8-12.

28. Yoshihiro T KK, Takahiko O,Yoshihisa K,Nobuyuki MI, Shigeaki Y,Shinsuke W, . Transcutaneous cisternal puncture for sampling of cerebral fluid in aweak rat. Exp Anim 2005; 54:193-196.

29. King DR, Cohn SM, Proctor KG. Changes in intracranial pressure, coagulation, and neurologic outcome after resuscitation from experimental traumatic brain injury with hetastarch. Surgery 2004 ; 136:355-363.

30. Klatzo I. Pathophysiological aspects of brain edema. Acta Neuropathol 1987; 72:236-239.

31. Fujimoto M, Takagi Y, Aoki T, Hayase M, Marumo T, Gomi M, et al. Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in focal cerebral ischemia. J Cereb Blood Flow Metab 2008; 28:1674-1685.

32. Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 2009 6; 158:983-994.

33. Shibnath Ghosal JL, Sushil K. Singh, Gautam Dasgupta, Joydeep Bhaduri, Mita Mukhopadhyay, Salil K. Bhattacharya. Chemistry of Shilajit, an immunomodulatory Ayurvedic rasayan. Pure Appl Chem (IUPAC) 1990; 62:1285 -1288.

34. Shibnath Ghosal JL, Sushil K. Singh, Gautam Dasgupta, Joydeep Bhaduri, Mita Mukhopadhyay, Salil K. Bhattacharya. Mast cell protecting effects of shilajit and its constituents. Phytother Res 1989; 3:249-252.

35. Park E, Bell JD, Baker AJ. Traumatic brain injury: can the consequences be stopped? CMAJ 2008; 178:1163-1170.

36. Faden AI. Microglial activation and traumatic brain injury. Ann Neurol 2011; 70:345-346.

37. Domowicz MS, Henry JG, Wadlington N, Navarro A, Kraig RP, Schwartz NB. Astrocyte precursor response to embryonic brain injury. Brain Res 2011; 1389:35-49.

38. Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, et al. Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol 2011; 70:374-383.

39. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 2004; 16:1-13.

40. Sarkaki AR, Khaksari M, Soltani Z, Shahrokhi N, Mahmoodi M. Time and dose dependent

Khaksari et al Shilajit and Traumatic Brain Injury

Iran J Basic Med Sci, Vol. 16, No. 7, Jul 2013



neuroprotective effects of sex steroid hormones on inflammatory cytokines after traumatic brain injury. J Neurotrauma 2011g 18.

41. Rooker S, Jorens PG, Van Reempts J, Borgers M, Verlooy J. Continuous measurement of intracranial pressure in awake rats after experimental closed head injury. J Neurosci Methods 2003; 131:75-81.

42. Rogatsky GG, Kamenir Y, Mayevsky A. Effect of hyperbaric oxygenation on intracranial pressure elevation rate in rats during the early phase of severe traumatic brain injury. Brain Res 2005; 1047:131- 016.

43. Oddo M, Levine JM, Mackenzie L, Frangos S, Feihl F, Kasner SE, et al. Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure. Neurosurgery 2011; 69:1037-0145.

44.Milde LN MJ, Michenfelder JD. Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs. Anesthesiology 1985; 63:371-377.

45. Lee H, Kim JM, Kim HJ, Lee I, Chang N. Folic acid supplementation can reduce the endothelial damage in rat brain microvasculature due to hyperhomocysteinemia. J Nutr 2005; 135:544-548.

46. Harsahay Meena HP, MC Arya, Zakwan Ahmed. Shilajit: A panacea for high-altitude problems. Int J Ayurveda Res 2010; 1:37-40.

47. B D. Materia Medica of Ayurveda. New Delhi: B Jain Publishers; 1991.

48. S. Ghosal JL, A. K. Jaiswal, S. K. Bhattacharya. Effects of shilajit and its active constituents on learning and memory in rats. Phytother Res 1993; 7:29-34.

49. S. K. Bhattacharya SG. Effect of Shilajit on rat brain monoamines. Phytother Res

1992; 6:163-164.

50. Shahlaie K, Boggan JE, Latchaw RE, Ji C, Muizelaar JP. Posttraumatic vasospasm detected by continuous brain tissue oxygen monitoring: treatment with intraarterial verapamil and balloon angioplasty. Neurocrit Care 2009; 10:61-69.

51. Jaeger M, Dengl M, Meixensberger J, Schuhmann MU. Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury. Crit Care Med 2010; 38:1343-137.