IMPACT OF MUMIJO (SHILAJIT) ON BLOOD COAGULATION PARAMETERS IN CHRONIC DOG EXPERIMENTS

ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 515 IMPACT OF MUMIJO (SHILAJIT) ON BLOOD COAGULATION PARAMETERS IN CHRONIC DOG EXPERIMENTS Mamadaliyev Sherzod Iminjon o‘g‘li - Assistant of Andijan State Medical Institute, Department of Pharmacology, Clinical Pharmacology, and Medical Biotechnology Egamberdiyev Jasur Jumanazar o‘g‘li - Assistant of Andijan State Medical Institute, Department of Pharmacology, Clinical Pharmacology, and Medical Biotechnology Abstract The present study investigated the effects of chronic administration of mumiyo at a dose of 100 mg/kg on the blood coagulation system in dogs. Five healthy adult animals were monitored over six days, and coagulation parameters were assessed at baseline and on days 3, 5, and 6. Mumiyo administration produced a significant prolongation of blood clotting time, plasma recalcification time, thrombin time, and heparin time, indicating a marked reduction in overall coagulation activity. Plasma tolerance to heparin increased progressively, suggesting enhanced sensitivity to anticoagulant modulation. Coagulation factors II and V exhibited time-dependent changes, with Factor II increasing steadily and Factor V showing an initial decrease followed by significant elevation. Fibrinogen levels increased moderately, while fibrinolytic activity decreased, reflecting slower clot degradation. Collectively, these findings demonstrate that mumiyo shifts hemostasis toward a hypocoagulable state and promotes the formation of looser, less stable clots. The results suggest potential anticoagulant properties of mumiyo and support the need for further studies to elucidate its mechanisms of action and therapeutic applicability. Keywords: Mumiyo, blood coagulation, hemostasis, anticoagulant activity, fibrinolysis, coagulation factors, chronic experiment. Introduction In traditional medical systems, Mumijo is classified as a herbomineral exudate with a rich ethnopharmacological background. It has been valued for centuries in diverse cultures across mountainous regions. Although widely associated with the Himalayas of India (1,3), Mumijo is also abundant in several territories of the former Soviet Union, including the Urals, Altai, Caucasus, Sayan Mountains, Baikal, Kazakhstan, Uzbekistan, and Tajikistan. Beyond these regions, deposits have been identified in China, Pakistan, Nepal, Afghanistan, and Tibet (4). Throughout history, this substance has been known by a variety of names: Shilajit or Silajita in Indian traditions; Asphalt in English; Silajatu in Bengali; Rock Juice in Tibetan medicine; Mountain Conqueror in Sanskrit; Hajarul-Musa or Arak-al-Jebal in Arabic; Mumiyo or Mumnae in Persian; μουμία in Greek; Muemu in Russian; Mumiyo in German; and other descriptors such as Mineral Resinous Bitumen, Jewish Bitumen, Mineral Wax, and Bragshun. Typically ranging in color from light brown to dark brown, Mumijo has been utilized for more than 3000 years as a rejuvenating substance and a potent adaptogen (2). The origin of Mumijo remains a subject of scientific debate, with three primary hypotheses proposed: the biological, geological, and bio-mineralogical theories. The biological hypothesis suggests that Mumijo forms from the decomposition of plant material or the metabolic excretions of animals under specific environmental and physicochemical conditions. The geological perspective interprets Mumijo as a byproduct of long-term geological transformations. Meanwhile, the bio-mineralogical concept integrates both organic and inorganic contributions, proposing that the final composition of ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 516 Mumijo is shaped by interactions between the precursor organic mass and the surrounding mineral environment. Factors such as local flora, geological substrate, soil properties, mineral composition, climate (temperature and humidity), altitude, and regional ecological conditions influence both the chemical profile and therapeutic potential of Mumijo (7). Despite sharing similar physical appearances across different geographic regions, the proportional representation of its components varies. Generally, Mumijo consists of 60–80% organic matter, 20–40% inorganic constituents, and trace elements including Fe, Ca, Cu, Zn, Mg, Mn, Mo, and P (8). Historical medical literature provides extensive documentation on the therapeutic applications of Mumijo. In the 10th century, the physician Ahvazi described its benefits in Kamāl as-Sanā’a, recommending it for cold-type headaches, hemoptysis, asthma, and aiding the expulsion of retained fetuses. Avicenna, in his seminal work The Canon of Medicine, praised Mumijo as a potent neurotonic agent capable of strengthening the brain, enhancing reproductive function, and treating a variety of disorders. By the 12th century, Jurjani’s Zakhire Khwārizmshāhi also highlighted its usefulness in managing inflammation, ulcers, urinary difficulties, and prostate conditions (5). Across diverse healing traditions, Mumijo has been administered in multiple dosage forms to manage a broad spectrum of ailments, including disorders of the urinary tract, jaundice, gallstones, gastrointestinal dysregulation, splenic enlargement, epilepsy, hypersensitivity reactions, neurological diseases, chronic bronchitis, tuberculosis, dermatological conditions such as eczema, anemia, and diabetes (9). However, concerns related to fungal contamination—particularly the presence of mycotoxins—pose a significant barrier to its global acceptance and clinical application (10). Traditional medicine practitioners continue to attribute numerous therapeutic properties to Mumijo, claiming efficacy in conditions such as reduced libido, nephrolithiasis, musculoskeletal pain, bone fractures, osteoarthritis, spondylitis, edema, hemorrhoids, age-related degeneration, wound antisepsis, metabolic disorders, and weight regulation (7). Modern pharmacological analyses support some of these claims, highlighting the anti-inflammatory, antioxidant, antimutagenic, and immunomodulatory activities largely associated with fulvic acid (FA) and humic acid (HA). These bioactive constituents have prompted interest in Mumijo as a potential chemopreventive agent (8). Experimental studies further demonstrate that Mumijo can lower blood glucose levels, improve lipid metabolism in animal models (11), enhance nucleic acid synthesis, and facilitate mineral transport to bone and muscle tissues (4). Additionally, Mumijo has been shown to increase both diuresis and natriuresis, supporting its traditional use in urinary and renal disorders (12). Materials and Methods The study was conducted on five clinically healthy adult dogs (n = 5) of both sexes, maintained under standard laboratory conditions. Animals were acclimatized for at least one week prior to experimentation. All procedures were carried out in accordance with ethical guidelines for the use of animals in biomedical research. A chronic experimental model was used to evaluate the effect of mumiyo on the blood coagulation system. Mumiyo was administered orally at a dose of 100 mg/kg body weight once daily throughout the experiment. Blood samples for coagulation analysis were collected at the following time points: • Baseline (before mumiyo administration) • Day 3 • Day 5 ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 517 • Day 6 Blood was drawn from the cephalic vein into tubes containing 3.8% sodium citrate (9:1 blood-toanticoagulant ratio). Samples were processed immediately after collection. Data were expressed as mean ± standard deviation (SD). Statistical comparisons between baseline and post-treatment values were performed using Student’s t-test for paired samples. Differences were considered statistically significant at p < 0.05. Results Administration of mumiyo at a dose of 100 mg/kg produced pronounced, time-dependent changes in the coagulation system of dogs throughout the chronic experiment. Table 1. Effect of mumiyo at a dose of 100 mg/kg on blood coagulation in dogs in chronic experiments (time in seconds, n = 5) Indicators Baseline data Days of blood sampling 3 5 6 Blood clotting time 193±68 354±60.0 475±26 436±37 Р <0.01 <0.01 <0.01 Plasma recalcification time 73±29 160±21 174±18 165±10 Р <0.01 <0.01 <0.01 Plasma tolerance to heparin 162±13 236±25 306±47 /0.01 Р < 0.05 <0.01 378±56 Heparin time 112±36 272±37 322±35 344±38 Р < 0.01 < 0.01 < 0.01 Factor II 23±1,2 27±2,0 35.6±3,2 40±4,7 Р >0,05 <0,05 <0,05 Factor V 16±0,7 14±0,8 17,7±1, 20±1,7 Р >0,05 <0,05 <0,05 Thrombin time 10±1,0 19±1,0 17±1,2 14±1,0 Р < 0.01 < 0.01 < 0.01 Fibrin (mg%) 371±26 455±27 400±32 425±38 Р <0,05 <0,05 <0,05 Fibrinolytic activity (min) 115±12,5 128±13 184±17 192±18 Р <0,05 <0,05 <0,05 Statistically significant differences (p < 0.05) compared with baseline values. Blood clotting time increased significantly from a baseline of 193 ± 68 s to 354 ± 60 s on day 3 (p < 0.01), reaching a maximum of 475 ± 26 s on day 5 (p < 0.01). By day 6 it remained elevated (436 ± 37 s, p < 0.01), indicating a sustained reduction in coagulation rate. A similar pattern was observed in plasma recalcification time, which more than doubled by day 3 (160 ± 21 s) and remained significantly elevated on days 5 and 6 (174 ± 18 s and 165 ± 10 s, respectively; all p < 0.01). ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 518 Plasma tolerance to heparin increased progressively, rising from 162 ± 13 s to 236 ± 25 s on day 3 (p < 0.05), 306 ± 47 s on day 5 (p < 0.01), and reaching 378 ± 56 s by day 6. This reflects an enhanced sensitivity of the coagulation system to heparin-like effects. Heparin time also showed a marked and statistically significant prolongation on all tested days, increasing from 112 ± 36 s initially to 272 ± 37 s, 322 ± 35 s, and 344 ± 38 s on days 3, 5, and 6, respectively (p < 0.01). Among the coagulation factors measured, Factor II (prothrombin) increased gradually and significantly after day 5: from 23 ± 1.2 units at baseline to 27 ± 2.0, 35.6 ± 3.2, and 40 ± 4.7 on days 3, 5, and 6. Significant differences (p < 0.05) were observed from day 5 onward. Factor V initially decreased slightly on day 3 (14 ± 0.8, p > 0.05), then significantly increased on days 5 and 6 (17.7 ± 1.0 and 20 ± 1.7, p < 0.05). Thrombin time increased sharply from 10 ± 1.0 s at baseline to 19 ± 1.0 s on day 3 (p < 0.01), then decreased slightly but remained significantly elevated on day 6 (14 ± 1.0 s, p < 0.01). The concentration of fibrinogen (reported as fibrin mg%) increased on day 3 (455 ± 27 mg%, p < 0.05), then fluctuated between 400–425 mg% on days 5 and 6, remaining significantly higher than baseline (p < 0.05). Fibrinolytic activity progressively increased, from 115 ± 12.5 min to 128 ± 13 min on day 3, and further to 184 ± 17 min and 192 ± 18 min on days 5 and 6 (p < 0.05), indicating a slowing of fibrin clot breakdown. Discussion The obtained results demonstrate that chronic administration of mumiyo at a dose of 100 mg/kg exerts a multidirectional but overall anticoagulant influence on the hemostatic system. The most prominent changes include significant prolongation of blood clotting time, plasma recalcification time, and thrombin time. These findings indicate a substantial decrease in the overall rate of thrombus formation. The consistent statistical significance (p < 0.01) across all timepoints suggests that mumiyo produces a stable, time-dependent anti-coagulant effect rather than transient fluctuations. The marked increase in plasma tolerance to heparin and prolongation of heparin time further support the conclusion that mumiyo enhances antithrombotic pathways, possibly by promoting endogenous anticoagulant activity or modifying the interaction between antithrombin and coagulation factors. Changes in coagulation factors also reflect a complex regulatory response. The transient decrease in Factor V followed by later elevation may indicate early consumption due to reduced coagulation efficiency, with subsequent compensatory upregulation. Meanwhile, the steady rise in Factor II (prothrombin) suggests increased synthesis or release during prolonged exposure to mumiyo; however, this did not correspond to increased clotting efficiency, likely because downstream steps of the coagulation cascade were inhibited, as evidenced by prolonged thrombin time. Fibrinogen concentrations increased moderately but remained within limits compatible with physiological compensation. Despite this, fibrinolytic activity decreased (indicated by prolonged lysis time), showing that fibrin clot breakdown slowed even as clot formation was also inhibited. This combined effect suggests an overall shift toward hypocoagulation with delayed fibrinolysis. Taken together, the data indicate that mumiyo exerts a systemic anticoagulating influence, likely through multiple mechanisms including slowed activation of intrinsic coagulation pathways, altered ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 519 responsiveness to heparin, and modulation of specific coagulation factors. The formation of looser clots observed clinically aligns with these laboratory findings. Conclusion The findings of this study demonstrate that chronic administration of mumiyo at a dose of 100 mg/kg produces a significant anticoagulant effect in dogs. This is evidenced by consistent prolongation of clotting-related times (blood clotting time, plasma recalcification time, heparin time, and thrombin time), increased plasma tolerance to heparin, and moderated changes in coagulation factors. Although fibrinogen levels rose moderately, fibrinolytic activity simultaneously decreased, indicating a slower rate of clot degradation. Overall, mumiyo induces the formation of looser, less stable clots and shifts the hemostatic balance toward a hypocoagulable state. These results suggest that mumiyo may possess therapeutic potential as a natural modulator of blood coagulation; however, further studies are needed to clarify the mechanisms involved and to evaluate safety and efficacy in broader biological settings. References 1. Ghosal S. 2006. Shilajit in Perspective. Narosa Publishing House, New Delhi India. 2. Olivieri MF, Marzari F, Kesel AJ, Bonalume L, Saettini F. Pharmacology and psychiatry at the origins of Greek medicine: The myth of Melampus and the madness of the Proetides. J Hist Neurosci. 2017;26(2):193-215. 3. Wilson E, Rajamanickam GV, Dubey GP,et al.2011. Review on shilajit used in traditional Indian medicine.J Ethnopharmacol 136:1–9 4. Schepetkin I, Khebnikov A, Kwon BS. 2002. Medical drugs from humus matter: focus on mumie.Drug Devel Res57: 140–159 5. Shirbeigi L ZA, Naghizadeh A, Alizadeh Vaghasloo M. The Concept of Temperaments in Traditional Persian Medicine. Trad Integr Med. 2017;2(3):143-56. 6. Frolova N, Kiseleva L, Tatiana. Chemical composition of mumijo and methods for determining its authenticity and quality (a review). Pharma Chem J. 1996;30(8):543-7. 7. Agarwal SP, Khanna R, Karmarkar R, Anwer MK, Khar RK. Shilajit: a review. Phytother Res. 2007;21(5):401-5. 8. Verma A, Kumar N, Gupta L, Chaudhary S. Shilajitin Cancer Treatment: Probable Mode of Action. Int J Pharmaceutic Bio Arch. 2016;7(1):12-6. 9. Stohs SJ, Singh K, Das A, Roy S, Sen CK. 12-Energy and Health Benefits of Shilajit. In: Bagchi D, editor. Sustained Energy for Enhanced Human Functions and Activity. Academic Press; 2017. p. 187-204 10. Ghosal S, Lal J, Singh SK, Goel RK, Jaiswal AK, Bhattacharya SK. The need for formulation of Shilajit by its isolated active constituents. Phytother Res. 1991;5(5):211-6 11. Trivedi N, Mazumdar B, Bhatt J, Hemavathi K. Effect of shilajit on blood glucose and lipid profile in alloxaninduced diabetic rats. Indian J Pharmacol. 2004;36(6):373-6. 12. Загрутдинов Ф.Ф., Мамадалиев Ш.И., Болтабоева Д.Ф. Влияние Среднеазиатских Видов Мумиё на диурез и натрий урез у Крыс. Open Herald: Periodical of Methodical Research. Volume 2, Issue 5, May, 2024, 12-14