ALAI MUMIYO (SHILAJIT): TRADITIONAL ORIGINS AND EXPERIMENTAL EVIDENCE OF ANTICOAGULANT AND FIBRINOLYTIC ACTIVITY

ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 77 ALAI MUMIYO (SHILAJIT): TRADITIONAL ORIGINS AND EXPERIMENTAL EVIDENCE OF ANTICOAGULANT AND FIBRINOLYTIC ACTIVITY Zagrutdinov Fanil Faridovich - Andijan State Medical Institute, Department of Pharmacology, Clinical Pharmacology, and Medical Biotechnology. Abstract The effect of Alai mumiyo extract (25 mg/kg) on blood coagulation in dogs was studied. Ten healthy animals received the extract orally, and coagulation parameters were measured at baseline, 30, and 60 minutes. The extract significantly prolonged clotting, recalcification, and thrombin times, increased plasma tolerance to heparin, and enhanced fibrinolytic activity (p < 0.05). Fibrinogen levels slightly decreased, while coagulation factor activities and total protein remained unchanged. Alai mumiyo exhibits anticoagulant and fibrinolytic effects, indicating potential for natural modulation of hemostasis. Keywords: Alai mumiyo, blood coagulation, dogs, anticoagulant activity, fibrinolysis, fibrinogen, thrombin time, natural extract. INTRODUCTION Traditional medicine (TM) encompasses a broad body of knowledge, skills, and healing practices developed and refined over generations within diverse cultures. Rooted in cultural beliefs, empirical observations, and accumulated experience, TM is employed for the preservation of health as well as for the prevention, diagnosis, and treatment of both physical and mental disorders (1). In recent decades, growing scientific interest in TM has led to an increasing number of studies examining the bioactive properties of natural substances used in these traditional systems, many of which have shown promising therapeutic and preventive potential (2). Traditional medicine comprises several distinct systems, including Traditional Persian Medicine (TPM), Traditional Arabic Medicine, Traditional Chinese Medicine (TCM), and Ayurveda, the traditional medical system of India (3). Among the many natural products employed in these traditions, Mumijo—also known worldwide under various names such as Shilajit (Hindi), Silajatu (Bengali), Rock Juice (Tibetan), Conqueror of Mountains (Sanskrit), Hajarul-Musa (Arabic), Moomiaii (Persian), Myemu (Russian), and Mumie (German)—occupies a unique position. This resinlike, paleto dark-brown substance, sometimes referred to as mineral pitch or mineral wax, has been valued for over 3,000 years for its rejuvenating, restorative, and adaptogenic properties (4). The origin of Mumijo has been interpreted through three principal theories: biological, geological, and bio-mineralogical. The biological theory suggests that Mumijo results from the slow decomposition of plant material and animal excretions under specific physicochemical conditions. The geological theory attributes its formation to long-term geological transformations, while the biomineralogical concept considers it a complex product formed when the organic precursors of Mumijo interact with mineral components of their environment. Factors such as local flora, rock and soil composition, altitude, temperature, and humidity influence the final chemical makeup and therapeutic potential of the substance (7). Despite regional differences, Mumijo generally contains 60–80% organic matter and 20–40% inorganic components, with trace elements including Fe, Ca, Cu, Zn, Mg, Mn, Mo, and P (8). ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 78 Historically, Mumijo has held an esteemed place in Persian medical literature. In the 10th century, Ahvazi’s Kamāl as-Sanā’a recommended its use for conditions such as cold headaches, hemoptysis, and asthma. Avicenna, in The Canon of Medicine, described Mumijo as a potent tonic for strengthening the brain, enhancing fertility, and treating various ailments. Later, in the 12th century, Jurjani’s Zakhire Khwārizmshāhi noted its benefits in treating inflammation, ulcers, and urinary and prostate disorders (5). Traditional healers have prescribed Mumijo in various doses for numerous health issues, including disorders of the urinary system, jaundice, gallstones, gastrointestinal disturbances, splenic enlargement, epilepsy, hypersensitivity, neurological conditions, chronic bronchitis, tuberculosis, eczema, anemia, and diabetes (9). However, fungal contamination and mycotoxin presence remain significant challenges to its broader therapeutic use (10). Practitioners of traditional medicine also attribute to Mumijo a wide spectrum of pharmacological effects—ranging from aphrodisiac and anti-inflammatory actions to applications in musculoskeletal disorders such as fractures, arthritis, and spondylitis. It is also used for edema, hemorrhoids, rejuvenation, wound healing, and metabolic regulation (7). The bioactive components of Mumijo, particularly fulvic and humic acids, are known for their antioxidant, anti-inflammatory, antimutagenic, and immunomodulatory activities, which may contribute to its proposed anticancer potential (8). Experimental studies further report reductions in blood glucose and improvements in lipid profiles in animal models (11), stimulation of nucleic acid synthesis, enhancement of mineral transport to muscle and bone (4), and promotion of diuresis and natriuresis (12). Taken together, these traditional and experimental findings suggest that Mumijo is a complex natural product with multifaceted biological activity and considerable potential for modern pharmacological investigation. Materials and Methods. The study was conducted on 10 clinically healthy adult dogs (n = 10) of both sexes, weighing 12–18 kg. All animals were maintained under standard vivarium conditions with free access to water and a balanced diet. The experimental protocol was approved by the Institutional Animal Ethics Committee and complied with international principles of humane animal treatment. The animals received an aqueous extract of Alai mumiyo orally at a dose of 25 mg/kg body weight. Blood samples were collected from the cephalic vein at three time points: before administration (baseline), 30 minutes after administration, and 60 minutes after administration. Venous blood was drawn into tubes containing 3.8% sodium citrate (9:1 ratio). The samples were centrifuged at 3000 rpm for 15 minutes to obtain platelet-poor plasma, which was used for coagulation tests. Data are presented as mean ± standard error of the mean (SEM). Differences between time points were evaluated using Student’s t-test. Differences were considered statistically significant at p < 0.05. Results Administration of the Alai mumiyo extract at a dose of 25 mg/kg caused marked changes in several indices of the blood coagulation system in dogs. The results are presented in Table 1. Table 1. Effect of Alai Mumiyo Extract at a Dose of 25 mg/kg on Some Blood Coagulation Parameters in Dogs (n = 10) (time in seconds unless otherwise stated) ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 79 Parameter Baseline After 30 min After 60 min Blood clotting time 354 ± 30 ↑900* ↑900* Plasma recalcification time 94 ± 10 134 ± 12 149 ± 13* Plasma tolerance to heparin 292 ± 34 473 ± 44* 425 ± 36* Thrombin time 13 ± 2.2 72 ± 15* 72 ± 15* Factor V activity 16 ± 0.5 17 ± 0.7 17 ± 0.5 Factor VII + X activity 35 ± 1.0 36 ± 1.4 38 ± 0.5 Fibrinogen (mg %) 330 ± 46 260 ± 34 290 ± 33 Fibrinolytic activity (min) 79 ± 4.5 90 ± 4.2 136 ± 11* Total protein (g %) 7.8 ± 0.3 7.8 ± 0.3 8.0 ± 0.3 Statistically significant differences (p < 0.05) compared with baseline values. A significant prolongation of blood clotting time was observed as early as 30 minutes after administration, increasing from 354 ± 30 to approximately 900 seconds (p < 0.05). This prolonged value persisted after 60 minutes, indicating a pronounced inhibition of the clotting process. The plasma recalcification time also increased significantly from 94 ± 10 to 149 ± 13 seconds by 60 minutes (p < 0.05), confirming a reduction in the overall coagulant activity of plasma. Similarly, the thrombin time was markedly prolonged from 13 ± 2.2 to 72 ± 15 seconds (p < 0.05), suggesting interference with fibrin formation or decreased fibrinogen conversion. An increase in plasma tolerance to heparin was observed, rising from 292 ± 34 to 425 ± 36 seconds (p < 0.05), indicating that mumiyo extract may enhance endogenous anticoagulant mechanisms or alter plasma heparin-binding properties. The activities of factors V and VII + X showed only minor, statistically insignificant elevations, suggesting that the primary site of the extract’s action lies outside the direct synthesis or activation of these coagulation factors. The fibrinogen concentration decreased moderately from 330 ± 46 mg% to 260 ± 34 mg% at 30 minutes, followed by a partial recovery to 290 ± 33 mg% after 60 minutes. This transient reduction might reflect increased fibrinolytic activity or consumption during delayed clot formation. Notably, the fibrinolytic activity increased significantly from 79 ± 4.5 to 136 ± 11 minutes (p < 0.05), which indicates enhanced breakdown of fibrin clots under the influence of mumiyo extract. The total plasma protein level remained stable throughout the observation period, confirming that the observed changes were specific to coagulation and not related to general protein metabolism. Discussion The results demonstrate that oral administration of Alai mumiyo extract in a dose of 25 mg/kg exerts a pronounced anticoagulant effect in dogs. The consistent prolongation of clotting, recalcification, and thrombin times, accompanied by increased fibrinolytic activity, suggests that the extract acts both on the coagulation and fibrinolytic systems. The prolongation of thrombin time indicates possible inhibition of fibrin polymerization or direct interference with thrombin activity. The observed enhancement of plasma tolerance to heparin may ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 80 reflect potentiation of the antithrombin-heparin complex or an increase in endogenous heparinoids. Together, these effects point to a systemic shift toward hypocoagulation. The mild decrease in fibrinogen concentration and the activation of fibrinolysis further support this hypothesis, indicating a stimulation of clot degradation processes. Similar properties have been reported for biologically active substances derived from natural mineral–organic complexes such as mumiyo, which contain humic acids, trace elements, and bioactive peptides capable of influencing enzyme systems. Overall, the findings suggest that Alai mumiyo possesses both anticoagulant and fibrinolytic activities. These effects may underlie its traditional use as a regulator of circulatory and metabolic functions. Further studies involving larger sample sizes, prolonged exposure, and isolation of active fractions are required to elucidate the precise mechanisms and potential therapeutic applications of this natural preparation. Conclusion The experimental data obtained indicate that administration of Alai mumiyo extract at a dose of 25 mg/kg produces a significant anticoagulant response in dogs. The extract markedly prolonged blood clotting, recalcification, and thrombin times while increasing plasma tolerance to heparin and enhancing fibrinolytic activity. These changes occurred without notable alterations in coagulation factor activities or total plasma protein levels, suggesting that the effect is mainly functional rather than due to depletion of coagulation components. Overall, Alai mumiyo demonstrates both anticoagulant and fibrinolytic properties, reflecting its potential to modulate hemostasis. The results support further investigation into its active constituents, mechanisms of action, and possible use as a natural regulator of blood coagulation and fibrinolysis. References 1. Qi Z, Kelley E. The WHO Traditional Medicine Strategy 2014-2023: A perspective. Science. 2014;346:S5-S6. 2. “WHO Traditional Medicine Strategy 2014-2023”. World Health Organization Retrieved 2014-0420. 2013. 3. Shahriari M, Zare F, Nimrouzi M. The Curative Role of Bitumen in Traditional Persian Medicine. Acta Med Hist Adriat. 2018;16(2):283-92. 4. 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. 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 ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 81 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