ETHNOPHARMACOLOGICAL RELEVANCE: Shilajit is a multi-component natural occurring mineral substance used in Ayurveda and Siddha systems of medicine which originated in India. Its source can be traced to the mountainous regions, where the hilly tribes first identified its beneficial use. Shilajit is aptly referred to as 'rasayana'/'rasayanam' in Ayurveda and Siddha literature which means rejuvenator because it prevents ailment and enhances the quality of life. MATERIALS AND METHODS: An attempt has been put forth to review shilajit pertaining to its origin, synonyms, varieties, physical properties, chemical constituents, therapeutic properties and important biological properties to affirm its rasayana property. All relevant information on shilajit was collected from classical texts including pharmacopoeias, formularies, etc. Moreover, select doctoral thesis from Banaras Hindu University, Varanasi and Gujarat Ayurved University, Jamnagar were also scanned. Published papers on shilajit were collected from important databases for biomedical sciences. Amongst, the various biological properties of shilajit, antioxidant activity and immuno-modulatory activity were focused as it is closely related to its rasayana potential. RESULTS: This review finds that shilajit is used in twenty Sastric formulations and twenty-four proprietary drugs for extraneous indications. Even-though, there is a long history of use of shilajit in traditional Indian materia medica, shilajit unfortunately lacks scientific evaluation and systematic documentation. In vivo antioxidant activity of shilajit has been studied at an irrelevant dose and without using a positive control. The immuno-modulatory activity does not stand the test of critical assessment and currently may be considered as unproven. CONCLUSION: Based on the earlier studies, the bioactivity of shilajit lacks substantial evidence. Nevertheless, further studies are imperative to overcome the lacuna in establishing the antioxidant property of shilajit and more specific assays are needed to vouch shilajit as an immuno-modulator which may be of use to establish its rasayana potential.

INTERVENTION: Intervention 1: Intervention group: The intervention group will receive two 500mg Shilajit capsules per day for two weeks. Intervention group will also receive medical treatments based on moderate COVID‐19 treatment protocols. Intervention 2: Control group: The control group will receive two placebo capsules per day for two weeks. Control group will also receive medical treatments based on moderate COVID‐19 treatment protocols. CONDITION: COVID‐19. ; COVID‐19, virus identified U07.1 SECONDARY OUTCOME: All‐cause mortality. Timepoint: any time during the study period. Method of measurement: Incidence of death due to any cause during the study period. Hospital admission duration. Timepoint: during the study period. Method of measurement: Days from admission to discharge or decease. Intensive Care Unit admission duration. Timepoint: during the study period. Method of measurement: Days from admission in the Intensive care unit to discharge or decease. Intensive Care Unit admission. Timepoint: During the study period. Method of measurement: Incidence of Intensive Care Unit admission. Time to Intensive Care Unit admission. Timepoint: During the study period. Method of measurement: Days from hospital admission to Intensive Care Unit referral. Time to ventilation. Timepoint: During the study period. Method of measurement: Days from admission to initiation of mechanical ventilation. Ventilation requirement. Timepoint: During the study period. Method of measurement: Incidence of ventilation requirement. INCLUSION CRITERIA: Diagnosis of moderate COVID‐19 disease (based on the World Health Organization laboratory and clinical criteria) Receiving standard and routine medications for moderate COVID‐19 based on management protocols for COVID‐19 age between 18 and 75 years old signing the written informed consent form PRIMARY OUTCOME: Axillary temperature. Timepoint: At the beginning of the study (before intervention initiation) and daily afterwards. Method of measurement: mercury thermometer. Duration of Intensive Care Unit admission. Timepoint: anytime during the study period. Method of measurement: Patient records data/Physician examination. Incidence of respiratory distress. Timepoint: At the beginning of the study (before intervention initiation) and anytime during the study period. Method of measurement: Patient records data/Physician examination. Intensive Care Unit admission. Timepoint: At the beginning of the study (before intervention initiation) and anytime during the study period. Method of measurement: Patient records data/Physician examination. Oxygen saturation:fraction of inspired oxygen ratio (SPO2:FiO2). Timepoint: At the beginning of the study (before intervention initiation) and 7, 14, and 28 days after Shilajit use. Method of measurement: Pulse oxymeter. Respiratory rate. Timepoint: At the beginning of the study (before intervention initiation) and daily afterwards. Method of measurement: Patient records data/Physician examination. Severity of clinical presentations of COVID‐19. Timepoint: At the beginning of the study (before intervention initiation) and 7, 14, and 28 days after Shilajit use. Method of measurement: The criteria proposed by the World Health Organization will be used to determine COVID‐19 severity and to assess the changes in disease severity during the study. Based on the criteria disease severity is defined based on a score between 0 and 8 as follows: (0) no clinical or virologic sign of infection (1) no limitation in activity (2) limitation in activity (3) hospital admission without oxygen therapy (4) hospital admission with oxygen therapy with mask or nasal cannula (5) hospital admission with non‐invasive oxygen therapy or high flow oxygen (6) hospital admission with intubation or mechanical ventilation (7) hospital admission with supported ventilation including extracorporeal membrane oxygenation, vasopressors, or renal replacement therapy (8) death. Time of death. Timepoint: anytime during the study period. Method of measurement: Patient records data/Physician examination. Ventilation need. Timepoint: At the beginning of the study (before intervention initiation) and anytime during the study period. Method of measurement: Patient records data/Physician examination.

INTERVENTION: Intervention1: Shilajit Rasayana Compound: 2 capsules 500mg each,twice a day with warm water for duration of 8 weeks Followed by follow up of 4 weeks in both groups with Placebo capsules of Barley flour Control Intervention1: COMPARATOR AGENT‐ BARLEY FLOUR CAPSULES AS PLACEBO : 2 capsules of 500mg,twice a day with warm water for duration of 8 weeks Followed by follow up of 4 weeks in both groups with Placebo capsules CONDITION: Diabetic Distal Symmetric Poly Neuropathy PRIMARY OUTCOME: Agnibala, Rogabala, and Chetasbala,Quality Of Life(WHO QoL) â?? BREF20, Biothesiometer for quantitative vibration assessment, Michigan Neuropathy Screening Instrument score (MNSI)and Modified Toronto Clinical Neuropathy Score‐‐‐‐‐‐Timepoint: 12 weeks (90) SECONDARY OUTCOME: HBA1c‐‐‐‐‐‐Timepoint: 90days INCLUSION CRITERIA: Metabolically stable Type 2 diabetic patients with symptomatic diabetic sensorimotorpolyneuropathy (DSPN) Patients of either sex between the age group 18â??80 years

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained.

UNLABELLED: The objective of the present study ( clinicaltrials.gov NCT02026414) was to observe the effects of oral supplementation of a purified and standardized Shilajit extract on skeletal muscle adaptation in adult overweight/class I obese human subjects from the U.S. POPULATION: Shilajit is a mineral pitch that oozes out of Himalayan rocks. The study design consisted of a baseline visit, followed by 8 weeks of 250 mg of oral Shilajit supplementation b.i.d., and additional 4 weeks of supplementation with exercise. At each visit, blood samples and muscle biopsies were collected for further analysis. Supplementation was well tolerated without any changes in blood glucose levels and lipid profile after 8 weeks of oral supplementation and the additional 4 weeks of oral supplementation with exercise. In addition, no changes were noted in creatine kinase and serum myoglobin levels after 8 weeks of oral supplementation and the additional 4 weeks of supplementation with exercise. Microarray analysis identified a cluster of 17 extracellular matrix (ECM)-related probe sets that were significantly upregulated in muscles following 8 weeks of oral supplementation compared with the expression at the baseline visit. This cluster included tenascin XB, decorin, myoferlin, collagen, elastin, fibrillin 1, and fibronectin 1. The differential expression of these genes was confirmed using quantitative real-time polymerase chain reaction (RT-PCR). The study provided maiden evidence that oral Shilajit supplementation in adult overweight/class I obese human subjects promoted skeletal muscle adaptation through upregulation of ECM-related genes that control muscle mechanotransduction properties, elasticity, repair, and regeneration.

BACKGROUND: Shilajit has been widely used remedy for treating a numerous of illness such as bone defects in Iran traditional folk medicine since hundreds of years ago. The aim of the present study was to explore the effect of Shilajit on the osteogenic differentiation of human adipose-derived mesenchymal stem cells (ASCs) in two- (2D) and three-dimensional (3D) cultures. MATERIALS AND METHODS: ASCs were seeded in 3D 1% alginate (Alg) hydrogel with or without Shilajit (500 µg/mL) and compared with 2D cultures. Then, characterization was done using electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), alkaline phosphatase (ALP) activity, alizarin red staining and Raman confocal microscopy. RESULTS: Adding Shilajit had no impact on the Alg scaffold degradability. In the 3D hydrogel and in the presence of osteogenic medium (OM), Shilajit acted as enhancer to increase ALP activity and also showed osteoinductive property in the absence of OM compared to the 2D matched groups at all time points (days 7 and 21 both P = 0.0006, for 14 days P = 0.0006 and P = 0.002, respectively). In addition, calcium deposition was significantly increased in the cultures exposed to Shilajit compared to 2D matched groups on days 14 (P < 0.0001) and 21 (P = 0.0003 and P = 0.003, respectively). In both 3D and 2D conditions, Shilajit induced osteogenic differentiation, but Shilajit/Alg combination starts osteogenic differentiation in a short period of time. CONCLUSION: As Shilajit accelerates the differentiation of ASCs into the osteoblasts, without changing the physical properties of the Alg hydrogel, this combination may pave the way for more promising remedies considering bone defects.

BACKGROUND: Shilajit is a safe, fluvic mineral complex exudate that is common to Ayurvedic medicine and is composed of fulvic acids, dibenzo-α-pyrones, proteins, and minerals. The purpose of this study was to examine the effects of 8 weeks of Shilajit supplementation at 250 mg·d- 1 (low dose) and 500 mg·d- 1 (high dose) versus placebo on maximal voluntary isometric contraction (MVIC) strength, concentric peak torque, fatigue-induced percent decline in strength, and serum hydroxyproline (HYP). METHODS: Sixty-three recreationally-active men ([Formula: see text] ± SD: 21.2 ± 2.4 yr.; 179.8 ± 6.3 cm; 83.1 ± 12.7 kg) volunteered to participate in this study. The subjects were randomly assigned to the high dose, low dose, or placebo group (each group: n = 21). During pre-supplementation testing, the subjects performed 2 pretest MVICs, 2 sets of 50 maximal, bilateral, concentric isokinetic leg extensions at 180°·s- 1 separated by 2-min of rest, and 2 posttest MVICs. Following 8 weeks of supplementation, the subjects repeated the pre-supplementation testing procedures. In addition, the groups were dichotomized at the 50th percentile based on pre-supplementation MVIC and baseline HYP. Mixed model ANOVAs and ANCOVAs were used to statistically analyze the dependent variables for the total groups (n = 21 per group) as well as dichotomized groups. RESULTS: For the upper 50th percentile group, the post-supplementation adjusted mean percent decline in MVIC was significantly less for the high dose group (8.9 ± 2.3%) than the low dose (17.0 ± 2.4%; p = 0.022) and placebo (16.0 ± 2.4%; p = 0.044) groups. There was no significant (p = 0.774) difference, however, between the low dose and placebo groups. In addition, for the upper 50th percentile group, the adjusted mean post-supplementation baseline HYP for the high dose group (1.5 ± 0.3 μg·mL- 1) was significantly less than both the low dose (2.4 ± 0.3 μg·mL- 1; p = 0.034) and placebo (2.4 ± 0.3 μg·mL- 1, p = 0.024) groups. CONCLUSIONS: The results of the present study demonstrated that 8 weeks of PrimaVie® Shilajit supplementation at 500 mg·d- 1 promoted the retention of maximal muscular strength following the fatiguing protocol and decreased baseline HYP. Thus, PrimaVie® Shilajit supplementation at 500 mg·d- 1 elicited favorable muscle and connective tissue adaptations.

Background Non-alcoholic fatty liver disease (NAFLD) is the main common cause of chronic liver disease. The aim of this study is to evaluate the effect of Shilajit, a medicine of Ayurveda, on the liver damage caused by NAFLD. Materials and methods Forty male Wistar rats, after being established as fatty liver models by feeding a high-fat diet (HFD, 12 weeks), were divided randomly into five groups as follows: control (standard diet), vehicle (HFD + distilled water), high-dose Shilajit (HFD + 250 mg/kg Shilajit), low-dose Shilajit (HFD + 150 mg/kg Shilajit) and pioglitazone (HFD + 10 mg/kg pioglitazone). The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), glucose and liver glutathione peroxidase (GPx), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, liver weight, and histopathological manifestation outcomes were measured after the 2-week intervention. Results Shilajit treatment significantly reduced the values of AST and ALT, TG, TC, LDL, glucose, liver weight, and steatosis, and instead, increased high-density lipoprotein (HDL) compared with the vehicle group (p < 0.05). Further, Shilajit treatment improved the adverse effects of HFD-induced histopathological changes in the liver as compared with the vehicle group (p < 0.001). MDA level and GPx activity increased but SOD activity decreased in the vehicle group compared with the control group (p < 0.05), while treatment with Shilajit restored the antioxidant/oxidant balance toward a significant increase in the antioxidant system in the Shilajit group (p < 0.05). Conclusions These findings suggest that Shilajit improved the histopathological NAFLD changes in the liver and indicated the potential applicability of Shilajit as a potent agent for NAFLD treatment.

Objective: Shilajit is a pale-brown to blackish-brown organic mineral substance available from Himalayan rocks. We demonstrated that in type I obese humans, shilajit supplementation significantly upregulated extracellular matrix (ECM)-related genes in the skeletal muscle. Such an effect was highly synergistic with exercise. The present study (clinicaltrials.gov NCT02762032) aimed to evaluate the effects of shilajit supplementation on skin gene expression profile and microperfusion in healthy adult females. Methods: The study design comprised six total study visits including a baseline visit (V1) and a final 14-week visit (V6) following oral shilajit supplementation (125 or 250 mg bid). A skin biopsy of the left inner upper arm of each subject was collected at visit 2 and visit 6 for gene expression profiling using Affymetrix Clariom™ D Assay. Skin perfusion was determined by MATLAB processing of dermascopic images. Transcriptome data were normalized and subjected to statistical analysis. The differentially regulated genes were subjected to Ingenuity Pathway Analysis (IPA®). The expression of the differentially regulated genes identified by IPA® were verified using real-time polymerase chain reaction (RT-PCR). Results: Supplementation with shilajit for 14 weeks was not associated with any reported adverse effect within this period. At a higher dose (250 mg bid), shilajit improved skin perfusion when compared to baseline or the placebo. Pathway analysis identified shilajit-inducible genes relevant to endothelial cell migration, growth of blood vessels, and ECM which were validated by quantitative real-time polymerase chain reaction (RT-PCR) analysis. Conclusions: This work provides maiden evidence demonstrating that oral shilajit supplementation in adult healthy women induced genes relevant to endothelial cell migration and growth of blood vessels. Shilajit supplementation improved skin microperfusion.

Objectives: Growing evidence showed involvement of vascular oxidative stress in the development of endothelial dysfunction, arterial stiffness and hypertension. Many clinical trials of antioxidants have proven unsuccessful in prevention of atherosclerosis and cardiovascular events. There is a need of new therapies that reduce age- and hypertension associated arterial stiffness in elderly individuals. We aimed to determine if shilajit (Asphaltum punjabianum), a natural phytocomplex which is immunomodulator, anti-inflammatory, antioxidant and antiaging, can reduce oxidative stress and improve arterial function in the elderly with hypertension. Materials and Methods: A parallel arm, open-label randomised controlled study was conducted on 60 elderly patients with hypertension. Study-group participants received shilajit (500 mg-twice/day for 30 days) with antihypertensives while control-group participants received only antihypertensive therapy. Oxidative stress, arterial stiffness and endothelial function markers were assessed at baseline and after 30 days of treatment. Results: Between-group analysis showed a significant decrease in oxidative stress markers: Malondialdehyde (P < 0.001) and oxidised-low-density lipoproteins (P = 0.015); and increase in total antioxidant capacity (P = 0.002), superoxide dismutase (P < 0.001) and reduced glutathione (P < 0.001) with complementary therapy of shilajit. There was no change in the markers of arterial stiffness and endothelial function. Conclusion: These findings suggest that shilajit may be of value as a natural antioxidant to reduce oxidative stress in elderly hypertension patients.