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Shilajitin Cancer Treatment: Probable Mode of Action

February 2016

Authors:

Akhilesh Verma

Banaras Hindu University

Neeraj Kumar

OPJU

Laxmi Narayan Gupta

Cancer is a horrible disease which is leadingcause of death after cardiovascular disease. The principal etiological factor for cancer comprise mutagens, toxins, free radicals, radiations apart from many other causes, inflammation can increase the threat of cancer development and progression. Indian medical system i.e.Ayurveda was used as a means for the prevention of the effects of aging and generation of disease. Shilajitis a potent rejuvenator and havingadaptogenic action. Since thousands of years many therapeutic assets have been ascribed to it, some pharmacological properties have been verified by modern scientific evaluation. Shilajit has been attributed with many miraculous restorative properties,improve the quality of life and it seemed to cure all diseases. Shilajit is a brownish-blackcoloredherbo-mineral medicine, collected from the high altitude mountains of many parts of the world. In this review we have focused on the cancer preventive and therapeutic properties of active principles ofShilajit. Shilajit possess anti-inflammatory, antioxidant, anti-mutagenic, immuno-modulator, antitumor, and photo-protective properties. These assets make Shilajit useful agents for cancer therapy and prevention.

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International Journal of Pharmaceutical & Biological Archives 2015; 7(1): 12 - 16

Shilajitin Cancer Treatment: Probable Mode of Action

Akhilesh Kr Verma*1, Neeraj Kumar2, L.N. Gupta3, Sunil Chaudhary4

1Research Scholar, Department of Rasa Shastra, Faculty of Ayurveda, IMS, BHU, India

2Professor, Department of Rasa Shastra, Faculty of Ayurveda, IMS, BHU, India

3Assistant Professor, Department of Rasa Shastra, Faculty of Ayurveda, IMS, BHU, India

4Assistant Professor, Department ofRadiotherapy & Radiation Medicine, IMS, BHU, India

Received 10Oct 2015; Revised 02Feb 2016; Accepted 13Feb 2016

ABSTRACT

Cancer is a horrible disease which is leadingcause of death after cardiovascular disease. The principal

etiological factor for cancer comprise mutagens, toxins, free radicals, radiations apart from many other

causes, inflammation can increase the threat of cancer development and progression. Indian medical

system i.e.Ayurveda was used as a means for the prevention of the effects of aging and generation of

disease. Shilajitis a potent rejuvenator and havingadaptogenic action. Since thousands of years many

therapeutic assets have been ascribed to it, some pharmacological properties have been verified by

modern scientific evaluation. Shilajit has been attributed with many miraculous restorative

properties,improve the quality of life and it seemed to cure all diseases. Shilajit is a brownish-

blackcoloredherbo-mineral medicine, collected from the high altitude mountains of many parts of the

world. In this review we have focused on the cancer preventive and therapeutic properties of active

principles ofShilajit. Shilajit possess anti-inflammatory, antioxidant, anti-mutagenic, immuno-modulator,

antitumor, and photo-protective properties. These assets make Shilajit useful agents for cancer therapy

and prevention.

Keyword: Shilajit, Adaptogenic, Anti-oxidant, Anti-inflammatory.

INTRODUCTION

Cancer is the leading cause of death after the

cardiovascular disease and is the major health

disaster, causing approximately 7 million deaths

every year worldwide. Now a daywe acquire

surgical intervention which is not able to cope up

effectively with this horrible disorder. The

conventional therapies i.e. chemotherapy,

radiotherapy, immunotherapy for cancer treatment

are not so efficient. Thus, there is a vital

obligatory to approaches for the cancer

management by natural agent like shilajit. Shilajit

is brownish black herbo-mineral compound

mainly composed of humic acid and fulvic acid.

Humic andfulvic acid have been well reported to

retain cancer preventive properties[1]. These

compounds can constrain mutagenesis and having

free radicals scavenging, photo-protecting and

anti-inflammatory properties that can prevent the

cancer progression. Shilajit is non-toxic, natural

compound which can be taken orally for

preserving good health. Therefore, it is necessary

that future clinical research work should focus on

phyto-constituents and pharmacological action of

shilajit in reference of cancer treatment as an

alternative. In this review, we address the use of

shilajit and its components for the inhibition and

controlling of cancer[2]. Shilajit is considered as a

vibrantmedicament in the ancient classics as

remedies and presently also extensively used by

the Ayurvedic physicians for a various

disorder.InAyurvedicclassical texts like

CharakaSamhitaand SusrutaSamhitadescribe the

use of shilajit as a treatment for all ailment of our

body as well as a rasayana (rejuvenative) to

increase the endurance[3]. Shilajitencompasses a

humic substance i.e. fulvic acid (FA) and humic

acid (HA) (60-80%), minerals (20-40%) and up to

5% of trace elements (Fe, Ca, Cu, Zn, Mg, Mn,

Mo, P)[4,5]. The chief and active constituents

responsible for the shilajit activities is the fulvic

acid and humic acid. By virtue of the FA shilajit

Akhileshet al. /Shilajit in Cancer Treatment: Probable Mode of Action

has many biological functions and uses [6, 7] which

acts as carrier molecule. The low molecular weight bioactive organic compound such as

oxygenated dibenzo-α-pyrones is also present in

shilajit. shilajit has been used for the treatment of

hypersensitivity, diabetes, digestive disorder,

nervous ailment, tuberculosis, chronic bronchitis,

asthma, anemia, eczema, bone fractures,

genitourinary ailment and many other diseases [8,

9] . The humic compounds of shilajit can be a

potential cancer preventive agent. Anti-

inflammatory, anti- oxidative, anti-mutagenic,

immuno-modulatory and several other effects of

shilajit have been already reported.

Pharmacological Actions of Shilajit

(Humic&FulvicAcid) in Cancer Prevention:

It is assumed that shilajit can play an important

role in cancer prevention and possibly in its

treatment. The general pharmacological actions of

shilajit in relation to cancer therapy are

summarized below.

Anti-Oxidant Properties:

Free radicals are molecules with incomplete

electron shells, which make them more chemically

reactive than those of complete electron shells.

Exposure to various environmental factors,

including tobacco smoke and radiation, can also

lead to free radical development. In humans, the

most extensive form of free radicals is oxygen.

When an oxygen molecule (O₂) becomes

electrically charged, it tries to take electrons from

other molecules, and thus can cause damage to

DNAproteins and cell membrane[10]. Such damage

specially damage in DNA could become

irreversible and might lead to illness including

cancer[11]. Antioxidants are substances that may

protect cells from the damage caused by unstable

molecules (free radicals) by neutralizing their

electrical charge and thus can prevent the free

radical damage in cells[11]. Free radicals which are

generated during cancer chemotherapy and

radiation therapy, can damage the normal cell

around the vicinity of the tumor cell, which makes

the cancer treatment rather painful. The anti-

cancer drugs damages the cellular DNA by

producing the reactive oxygen species (ROS)

hence the antioxidants can be used with the cancer

therapy to reduce the pain and the severity of the

side effects [11]. HA compound are brilliant

antioxidantsalong with anti-lipid per-oxidative

activity [12]. Shilajit has free radical scavenging or

antioxidant properties against the NO &OH and

this antioxidant activity depends on the increasing

concentration of the humic compounds present in

shilajit[01]

Anti-Inflammatory Properties:

The inflammation is measured to induce the

cancer progression, development and the

metastasis [10]. It has been shown that the HA

matters has anti-inflammatory properties [01].

Shilajit has anti-inflammatory properties

confirmed in the study of the Goel et al[13]. They

have shown that the shilajit can reduce the

inflammation such as pedal oedema and

granuloma pouch in rats induced by the

carrageenan. In addition, shilajit can also reduce

the adjuvant induced arthritis in rats. In another

study the humic compounds derived from the coal

was found to inhibit the inflammation responded

ear swelling in the rats [14]. Lowen et al have

described that HA alone or HA combined with

other anti-inflammatory drugs such as

indomethacin were beneficial for the chronic and

acute inflammation in the male

SparagueDwleyrats[15]. Van Rensburg et al have

shown that the presence of potassium humate

reduces the level of pro-inflammatory cytokines

like TNF-α, IL-1β, IL-6 and IL-10 produced by

mononuclear cells and also the compliment

activation[16]. HA can inhibit the degranulation of

the neutrophils during inflammation, moreover it

is an anti-allergic agent [17,18]. It has been

oxifulvic acid may be beneficial in the clinical

treatment of inflammatory skin conditions in

humans as, FA possesses anti-inflammatory

properties [19].

Photo Protective Properties:

The exposure to the radiation as the ultraviolet

(UV) rays can leads to the long-term DNA

damage by forming the thymine dimer in the

DNA which can lead to mutations and cancer.

Shilajit can function as photo-protective agent, as

reviewed by Meena et al 2010[20]. The humic

compounds have been proved to be excellent

agents for reduction of gene mutation caused by

pollutants and mutagens. Toxins, pesticides,

radioactive metals, petroleum products,

polyaromatic hydro-carbons and heavy metals can

be inactivated by HA[21]. Moreover, it reduces

bioavailability of the hazardous matters and averts

the formation of the mutagenic or carcinogenic

compound and prevent DNA damage in the

cell[22]. Marova et al have shown that processed

HA can inactivate the mutagens which were tested

on the yeast[23]. They used 4-nitroquinoline-N-

oxide (4-NQO), a mutagen on Saccharomyces

cerevisiae D7 to check the anti-mutagenic

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Akhileshet al. /Shilajit in Cancer Treatment: Probable Mode of Action

properties of the sodium or potassium humate and

found that the sodium humate have significant

anti-mutagenic property against the 4-NQO.

Furthermore, Zhang et al checked the toxicity and

bioavailability of the ionic liquids (ILs), 1-butyl-

3-methylimidazolium chloride and 1-octyl-3-

methylimidazolium chloride, in the presence of

the HA [24]. These results illustrated that the HA

reduces the bioavailability and toxicity of these

two ILs and also HA increases the viability

around 50% of HepG2 cell line against the two

ILs.It has been shown that HA possesses

significant cytotoxic activity in the CEM (acute T

lymphoblastic leukaemia) cell line[25]. HA have

been found to exert anti-proliferative action and

growth inhibition on HL-60 cells through

induction of apoptosis by activating the caspase-3

and mitochondrial cytochrome-c in these cells [26].

HA has also been found to induce the apoptosis

and inhibit the growth in the human smooth

muscle cells. Hseu et al, have reported that HA

has been found to inhibit the proliferation of the

smooth cells in the G1 phase of the cell cycle and

led to the apoptotic cell death of smooth muscles

cells [27]. Shilajit and HA matters are immune-

modulatoryagents[28]. Shilajit helps the immune

system for increased cytokine production by

activated immunological cells and maintains the

cell integrity [29]. All biological molecules are

prone to oxidative damage by free radicals such as

reactive oxygen species (ROS) and reactive

nitrogen species (RNS). This oxidative damage

leads to various diseaseconditions, viz., heart

disease[30],autism[31],cancer[32,33],diabetes

[34],Arthritis[35],Alzheimer’sdementia[36],Parkinson

’sdisease[37],cataracts[38],andaging[39]. Antioxidants

are the compounds that prevent thisoxidative

damage by different mechanisms [40]however

synthetic antioxidants possess adverse effects[41].

Immuno-Modulatory Activity:

Shilajit as an immune-modulator agent was

studiedin mice that were given either shilajit

extract or a placebo.The white blood cell activity

was studied and monitored at intervals after

receiving the shilajit extract or a placebo. It was

found that the white blood cell activity was

increased after administration ofshilajit extract.

The activity increased as the dose of shilajit

extract and time of exposure was increased [42].

Shilajit and its combined constituents elicited and

activated to different degrees, murine peritoneal

macrophages and activated splenocytes of tumor-

bearing animals at early and later stages of tumor

growth. In another experiment, the effect of

shilajit was determined on the levels of brain

monoamines in rats. It was found that shilajit at a

dose of 25 and 50 mg/kg i.p. for 5 days

significantly reduced the level of 5-hydoxy

tryptamine and 5-hydroxy indole acetic acid and

increased the level of dopamine, noradrenaline

and their metabolites in rat brain. These changes

in neurotransmitter levels are similar to those seen

in cases of increased humoral (immune) activity

and hence validate its use as an

Ayurvedicrasayana. [43].

Ayurvedic View:

The CarakaSamhitadeliberatesshilajit in a chapter

as rejuvenation therapy (rasayana). It has been

suggested that the contemporary ofrasayana is an

adaptogenic substance [44].The

CarakaSamhitastates that there is no curable

disease in the universe, which is not effectively

cured by shilajit when it is administered at the

appropriate time, combination with suitable drugs

and by adopting the prescribed method. When

administered to a healthy person, with similar

conditions it produces immense energy. In the

SushrutaSamhita, it is noted that there is no

physical distemper, which does not yield by

highly therapeuticqualities of shilajit. When

gradually taken, (in adequate doses) it tends to

improve the strength and complexion of the

body[45].The ancient Ayurvedictext

AstanaHrdayam also states that it is the best

rejuvenator [46].

CONCLUSION

Humic and fulvic acid have been reported to

possess cancer preventive properties. It has been

shown that these compounds can inhibit

mutagenesis and have free radicals scavenging,

photo-protecting, anti-inflammatory and toxic

compound removing properties that can inhibit the

cancer development. Shilajit is non-expensive,

non-toxic compound which can be taken orally.

Therefore, it is rational that future clinical studies

should focus on examining the efficacy of

Shilajitand its active constituents in cancer

prevention as an alternative pharmacological

agents. In this review, we address the use of

Shilajit and its constituents for the prevention and

management of cancer. Shilajit is one such

compound, which has been used in Ayurveda for

centuries. The humic compounds of Shilajit can

be a potential cancer preventive agent. Anti-

inflammatory, anti- oxidative, anti-mutagenic,

immuno-modulatory and several other effects of

Shilajit have been already reported.

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Akhileshet al. /Shilajit in Cancer Treatment: Probable Mode of Action

REFERENCES

1. Peña-Méndez EM, Havel, J, Patočka J.

Humic substances - compounds of still

unknown structure: applications in

agriculture, industry, environment, and

biomedicine. Appl Biomed. 2005; 3:13-24.

2. Kishor Pant, Bimala Singh, Nagendra

Thakur; Shilajit: A Humic Matter Panacea

for Cancer International Journal of

Toxicological and Pharmacological

Research 2012; 4(2): 17-25.

3. Talbert R. Shilajit a materiamedica

monograph, Degree paper Grass Valley,

California: California College of

Ayurveda; 2004.

4. Ghosal S, Lal J, Singh SK. The Core

Structure of Shilajit Humus. Soil

BiolBiochem. 1991;23:673–80.

5. Frolova LN, Kiseleva TL. Chemical

Composition of Mumie and Methods for

Determination of Its Authenticity and

Quality. ChemPharm J. 1996;8:49–53.

6. Ghosal S, Singh SK, Kumar Y, Srivastava

RS, Goel RK Dey, Bhattacharya SK. Anti-

Ulcerogenic Activity of Fulvic Acids and

4′-Methoxy-6-Carbomethoxybiphenyl

Isolated From Shilajit. Phytother Res.

1988;2:187-91.

7. Schepetkin I, Khlebnikov A, Kwon BS.

Medical Drugs From Humus Matter:

Focus on Mumie. Drug Dev Res.

2002;57:140-59.

8. Goel RK, Banerjee RS, Acharya SB.

Antiulcerogenic and Antiinflammatory

Studies WithShilajit. J Ethnopharmacol.

1990;29:95-103.

9. Acharya SB, Frotan MH, Goel RK,

Tripathi SK, Das PK. Pharmacological

Actions of Shilajit. Indian J Exp Biol.

1988;26:775-77.)

10. Wiseman H, Halliwell B. Damage to DNA

by reactive oxygen and nitrogen species :

role in inflammatory disease and

progression to cancer. Biochem J 1996;

313:17-29.

11. Borek C. Dietary Antioxidants and Human

Cancer. Integrative cancer therapies

2004;3(4):333-41.

12. Schepetkin IA, Khlebnikov AI, Ah SY,

Woo SB, Jeong CS, Klubachuk ON, Kwon

BS. Characterization and Biological

Activities of Humic Substances from

Mumie. J Agric Food Chem

2003;51:5245-54.

13. Goel RK, Banerjee RS, Achrarya SB.

Antiulcerogenic and antiinflammatory

studies with Shilajit. J Ethnopharmacol.

1990;29:95-103.

14. Van Rensburg CEJ, Snyman J R, Mokoele

T, Cromarty A D. Brown Coal Derived

Humate Inhibits Contact Hypersensitivity;

An Efficacy, Toxicity and Teratogenicity

Study in Rats. Inflammation. 2007;30(5).

15. Lown JF, Gill K, Cutler SJ, Cutler HG,

Pollock SH, inventor; Anti-inflammatory

humate compositions and metohs of use

thereof. Dallas, TX (US)2006.

16. Van Rensburg CEJ, and Naude PJ.

Potassium Humate Inhibits Complement

Activation and the Production of

Inflammatory Cytokines In Vitro.

Inflammation. 2009;32(4):270-76.

17. Gisela K, Elizabeth C, Rensburg JV. An In

Vitro Investigation of the Anti-

Inflammatory Properties of Potassium

Humate.Inflammation. 2004; 28:169-74.

18. Amada PY, Isoda H, Yamaguchi T,

Talorete TPN, Abe Y. Inhibitory Effect of

Fulvic Acid Extracted from Canadian

Sphagnum Peat on Chemical Mediator

Release by RBL-2H3 and KU812 Cells. .

BiosciBiotechnolBiochem 2007; 71:1294-

305.

19. Van Rensburg CEJ, Malfeld SCK, Dekker

J. Topical Application of Oxifulvic Acid

Suppresses the Cutaneous Immune

Response in Mice. Drug development

research. 2001; 53:29-32.

20. Meena H, Pandey HK, Arya MC, Ahmed

Z. Shilajit: A panacea for high-altitute

problems. International Journal of

Ayurveda Research. 2010;1(1):37-40.

21. Yates LM, Wandruszka, R.V.

Decontamination of Polluted Water by

Treatment with CrudeHumic Acid Blend.

Environ Sci Technol. 1999; 33:2076-80.

22. Perminova IV, Hatfield, K. Remediation

Chemistry of Humic Substances: Theory

and Implications for Technology. In:

Perminova IV, editor. Use of Humic

Substances to Remediate Polluted

Environments: From Theory to

Practice.NetherlandS: Springer; 2005; 3-

36.

23. Marova I, Kucerik J, Duronova K,

Mikulcova A, Vlckova Z. Antimutagenic

IJPBA, Jan - Feb, 2016, Vol. 7, Issue, 1

Akhileshet al. /Shilajit in Cancer Treatment: Probable Mode of Action

and/or genotoxic effects of processed

humic acids as tested upon S. cerevisiae

D7. Environ ChemLett 2011; 9:229-33.

24. Zhang Z, Liu J, Cai X, Jiang W, Luo W.

Jiang G. Sorption to Dissolved Humic

Acid and Its Impacts on the Toxicity of

Imidazolium Based Ionic Liquids. Environ

Sci Technol. 2011;45:1688-94.

25. Vašková J, Veliká B, Pilátová M, Kron I,

Vaško L. Effects of humic acids in vitro.

In Vitro CellDevBiol-Animal.

2011;47:376-82.

26. Yanga HL, HseuYC, Yi-Ting Hseua, Luc

FJ, Linb E, Laid JS. Humic acid induces

apoptosis in human premyelocytic

leukemia HL-60 cells. fe Sciences.

2004;75(15):1817-31.

27. Hseu YC, Lin E, Chen JY, Liua R, Huang

CY, Lu FJ, Liao JW, Chen SC, Yang HL.

Humic Acid Induces G1 Phase Arrest and

Apoptosis in Cultured Vascular Smooth

Muscle Cells. Environmental Toxicology.

2008; 24:243-58.

28. Schepetkin IA, Khlebnikov AI, Ah SY,

Woo SB, Jeong CS, Klubachuk ON, Kwon

BS. Characterization and Biological

Activities of Humic Substances from

Mumie. J Agric Food Chem

2003;51:5245-54.

29. Ghosal S. Chemistry of Shilajit, an

immunomodulatoryAyurvedicrasayan.

Pure &ApplChern. 1990;62(7):1285-88.

30. Singh U, Jialal I. Oxidative stress and

atherosclerosis. Pathophysiology 2006; 13:

129-142.

31. Chauhan A, Chauhan V. Oxidative stress

in autism. Pathophysiology 2006; 13: 171-

181.

32. Babbs CF. Free radicals and the etiology

of colon cancer. Free Radical Biol Med

1990; 8: 191-200.

33. Sun Y. Free radicals, antioxidant enzymes

and carcinogenesis. Free Radical Biol Med

1990; 8: 583-599.

34. Jain SK, McVie R, Bocchini JA.

Hyperketonemia (ketosis), oxidative stress

and type 1 diabetes. Pathophysiology

2006; 13:163-170.

35. Mahajan A, Tandon VR. Antioxidants and

rheumatoid arthritis. J Indian

RheumatolAssoc 2004; 12: 139-142.

36. Chauhan V, Chauhan A. Oxidative stress

in Alzheimer’s disease. Pathophysiology

2006; 13: 195-208.

37. Sudha K, Rao AV, Rao S, Rao A. Free

radical toxicity and antioxidants in

Parkinson’s disease. Neurol India 2003;

51(1): 60-62.

38. Vinson JA. Oxidative stress in cataracts.

Pathophysiology 2006; 13: 151-162.

39. Dizdaroglu M, Jaruga P, Birincioglu M,

Rodriguez H. Free radical-induced damage

to DNA: Mechanisms and measurement.

Free Radical Biol Med 2002; 32(11):

1102-1115.

40. Bergendi L, Benes L, Durackova Z,

Ferencik M. Chemistry, Physiology and

pathology of free radicals. Life Sci 1999;

65(18/19): 1865-1874.

41. Chanda S, Dave R. In vitro models for

antioxidant activity evaluation and some

medicinal plants possessing antioxidant

properties: An overview. Afr J Microbiol

Res 2009; 3(13): 981-996.

42. Bhaumik S, Chattapadhay S, Ghosal S.

1993. Effects of Shilajit on mouse

peritoneal macrophages. Phytother Res 7:

425– 427.

43. Ghosal S. 1990. Chemistry of Shilajit, an

immunomodulatoryAyurvedicrasayan.

Pure ApplChem (IUPAC) 62: 1285–1288.

44. Ghosal S, Lal J, Srivastava RS,

Bhattacharya SK, Upadhyay SN, Jaiswal

AK, Chattopadhyay U.

Immunomodulatory and CNS effects of

sitoindosides IX and X. Phytotherapy Res

1989; 3: 201-6.

45. Bhishagratna KK. SusrutaSamhitaVol 2,

Chapter XIII. Varanasi, India:

Chowkhamba Sanskrit Series Office,

Varansi-1, 1998.

46. Murthy, KRS. AstangaHrdayam. 5th

edition. Krishnadas Academy, Varanasi,

India, 2001.

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Mar 2022

Objective: To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD). Methods: After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated. Results: After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05). Conclusion: The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.

Effect of humic acids on lead poisoning in bones and on a subcellular level in mitochondria

Article

Full-text available

Nov 2020
ENVIRON SCI POLLUT R

Humic acids (HA) are natural substances which exhibit a remarkable spectrum of health benefits, such as their role in chelation. This study aims to supplement the current knowledge on the chelating effects of HA in chronic lead intoxication in rat femurs and in liver, heart and kidney mitochondria in an experiment lasting 10 weeks. Lead acetate trihydrate was administered to rats for 5 weeks at a daily dose of 155.5 mg/kg body weight. At the same time, rats were given three concentrations of HA, with their effect measured over the following 5 weeks. Increased Pb concentrations were detected in the femur after the first week, while HA-administered groups showed a tendency towards inhibiting the increase in Pb deposition. After 5 weeks, Pb concentrations dropped significantly in the HA groups. At the same time, however, other elements were redistributed, with a decrease in Se and Zn being particularly noteworthy. While an increase in Pb concentrations was found after 5 weeks of Pb administration, a concentration of 1% HA resulted in the least significant increase in Pb as well as an increase/decrease in Se/Cu, respectively. In mitochondria, an increase in Pb content was detected after the first and fifth weeks with concomitant redistribution of other elements. At the end of the experiment, again in the 1% HA group, Pb concentrations remained higher only in the liver with the other elements sufficiently normalized, indicating this concentration to be useful in the treatment of Pb intoxication.

In vivo study of Nephroprotective potential of Shilajit by using Cisplatin induced nephrotoxicity model

Article

Sep 2018

Hazardous or Advantageous: Uncovering the Roles of Heavy Metals and Humic Substances in Shilajit (Phyto-mineral) with Emphasis on Heavy Metals Toxicity and Their Detoxification Mechanisms

Article

Full-text available

Feb 2024
BIOL TRACE ELEM RES

Shilajit is a phyto-mineral diffusion and semi-solid matter used as traditional medicine with extraordinary health benefits. This study provides a comprehensive data on Shilajit with emphasis on heavy metal profile, associated toxicities, and metal detoxification mechanisms by humic substances present in Shilajit. Data was searched across papers and traditional books using Google Scholar, PubMed, Science Direct, Medline, SciELO, Web of Science, and Scopus as key scientific databases. Findings showed that Shilajit is distributed in almost 20 regions of the world with uses against 20 health problems as traditional medicine. With various humic substances, almost 11 biological activities were reported in Shilajit. This phyto-mineral diffusion possesses around 65 heavy metals including the toxic heavy metals like Cu, Al, Pb, As, Cd, and Hg. However, humic substances in Shilajit actively detoxify around 12 heavy metals. The recommended levels of heavy metals by WHO and FDA in herbal drugs is 0.20 and 0.30 ppm for Cd, 1 ppm for Hg, 10.00 ppm for As and Pb, 20 ppm for Cu, and 50 ppm for Zn. The levels of reported metals in Shilajit were found to be lower than the permissible limits set by WHO and FDA, except in few studies where exceeded levels were reported. Shilajit consumption without knowing permissible levels of metals is not safe and could pose serious health problems. Although the humic substances and few metals in Shilajit are beneficial in terms of chelating toxic heavy metals, the data on metal detoxification still needs to be clarified.

Humic substance - Compounds of still unknown structure: Applications in agriculture, industry, environment, and biomedicine

Article

Full-text available

Jan 2005

Humic substances as part of humus-soil organic matter - are compounds arising from the physical, chemical and microbiological transformation (humification) of biomolecules. They are important because they constitute the most ubiquitous source of non-living organic material that nature knows. Approximately 80% of the total carbon in terrestrial media and 60% of the carbon dissolved in aquatic media are made up of humic substances. Humic substances have important roles in soil fertility, and are considered to have primal relevance for the stabilization of soil aggregates. They can be divided into three components according to their solubility: humic acids, fulvic acids and humin. Humic acids are the most explored group of humic substances. Beyond their relevance for life these substances have industrial applications in the development of absorbents to be used at the sources of metal-poisoning. Being natural substances, their purification process is cheaper than the synthesis of any other sorbent and, moreover, due to their high operability, they absorb more than the absorbents used to date, such as active charcoals or clays. The specific properties of humic acid products enable their application in industry, agriculture, environmental and biomedicine.

Use of Humic Substances to Remediate Polluted Environments: From Theory to Practice: Proceedings of the NATO Advanced Research Workshop on Use of Humates to Remediate Polluted Environments: From Theory to Practice Zvenigorod, Russia 23–29 September 2002

Book

Jan 2005

Effective remediation of polluted environments is a priority in both Eastern and Western countries. In the U.S. and Europe, remediation costs generally exceed the net economic value of the land. As a result, scientists and engineers on both sides of the Atlantic have aggressively tried to develop novel technologies to meet regulatory standards at a fraction of the costs. In situ remediation shows considerable promise from both technical and economic perspectives. In situ technologies that deploy natural attenuating agents such as humic substances (HS) may be even more cost effective. Numerous studies have shown humics capable of altering both the chemical and the physical speciation of the ecotoxicants and in turn attenuate potential adverse environmental repercussions. Furthermore, the reserves of inexpensive humic materials are immense. Which suggests HS portend great promise as inexpensive amendments to mitigate the environmental impacts of ecotoxicants and as active agents in remediation. To elucidate emerging concepts of humics-based remediation technologies, we organized the NATO Advanced Research Workshop (ARW), entitled "Use of humates to remediate polluted environments: from theory to practice", held on September 23-29, 2002 in Zvenigorod, Russia (see the web-site http://www.mgumus.chem.msu.ru/arw).

Oxidative stress and aging

Article

Aug 2013

The role of free radicals in aging process has been the centre of research for sometimes. It is assumed that with aging, damaging effects of oxygen free radicals possibly accumulate on all cellular components, especially the DNA and the mitochondria. In addition, because of the decreased efficiency of the antioxidant systems, the oxidative mechanisms prevail in numerous age-dependent diseases, such as arteriosclerosis, Parkinsonism and Alzheimer disease. The present study was aimed at revealing an eventual correlation between the oxidative balance and nutritional profile and/or psychopathological status in elderly population living in a small country, Orria (SA). Sixteen out of 24 subjects over ninety-year-old (2.36% of the country's population), were studied. Nine (56%) of them were females with mean age of 93.4 (SD 2.44) years. The psycho-physical state of the subjects was estimated by means of the mini mental state examination (MMSE), activities of daily living (ADL) and instrumental activities of daily living (IADL). The nutritional state and the physical activity of the subjects were evaluated through the mini nutritional assessment (MNA). All studied parameters underwent a correlation analysis of Pearson. An excessive oxidative stress possibly influenced the psychophysical state of the elderly, which subsequently exerted negative effects on the quality of life as well as the life span of the subjects. Although it is difficult to define the exact role of free radicals in aging process, yet the levels of free radicals may be considered as true "marker" accompanying aging process.

Shilajit: A humic matter panacea for cancer

Article

Jan 2012

Cancer is the leading cause of death after cardiovascular disease. The primary etiologic agents for cancer include mutagens, toxins, free radicals, heavy metals, blood sugar, virus, radiations apart from many other factors including inflammation which can increase the risk of cancer development and progression. Shilajit is a blackish-brown coloured herbomineral medicine, collected from the high altitude mountains of many parts of the world. Shilajit refers to the humic matter that contains 60-80% of fulvic acid (FA) and humic acid (HA). The biological activity of Shilajit is mainly attributed to these humic compounds HA and FA. In this review we have focused on the cancer chemopreventive and therapeutic properties of Shilajit and humic compounds. Shilajit and HA possess anti-inflammatory, antioxidant, antimutagenic, antitoxic, antiviral, heavy metal chelating, antitumor, apoptotic and photo-protective properties. These properties make Shilajit useful agents for cancer therapy and prevention. In addition, Shilajit has no reported side effects and can be administered as a nutritive and rejuvenating tonic and combats age related problems.

Role of free radicals in the etiology of colon cancer

Article

Dec 1990
FREE RADICAL BIO MED

Charles F. Babbs

Antioxidants and rheumatoid arthritis

Article

Jan 2004

Chemistry of Shilajit, an immunomodulatory Ayurvedic rasayan

Article

Jul 1990
PURE APPL CHEM

Shibnath Ghosal

The chemical polemics in the reported literature on shilajit are resolved. This study shows that humification of latex and resin-bearing plants is responsible for the major organic mass (80-85%) of shilajit. The low mol. wt. chemical markers (&lo%), viz. aucuparins, oxygenated dibenzo-K -pyrones and triterpenic acids of the tirucallane type (free and conjugated), occurring in the core structure of shilajit humus, are the major active constituents of Himalayan shilajit. The therapeutic effects of shilajit are the consequences of hormonal control and regulation of immunity.

Decontamination of Polluted Water by Treatment with a Crude Humic Acid Blend

Article

May 1999

The use of humic acid for contaminant extraction from environmental matrices is an attractive concept because of the natural origin of the material and its low pollution potential. The problem of availability and the need for alkaline extraction were circumvented by the use of an unrefined leonardite humic acid (LHA) material used as received. This mined product has a high humic acid content, is inexpensive, and is available in bulk. LHA, applied without alkaline extraction, was used in the decontamination of water containing organic and inorganic test pollutants. The former included pyrene, difenzoquat, and rhodamine B base, while the latter were comprised of Pb2+, Zn2+, Ni2+, Cu2+, Sr2+, Cd2+, As3+, Ag+, and Mg2+. Simulated acidic waste solutions were treated by both batch precipitation and column extraction, with the pollutants applied singly and as mixtures. In the precipitation procedure, commercial lime was used as the coagulant, and virtually complete removal of the metals was achieved. Pyrene and difenzoquat were also removed, but rhodamine B base was not. With LHA column elution, all three organic compounds were fully extracted from waste solutions, including those containing mixed contaminants. Removal of metals by column treatment gave encouraging results, with Pb2+, Cu2+, and Sr2+ being extracted most effectively.

Topical application of oxifulvic acid suppresses the cutaneous immune response in mice

Article

May 2001
DRUG DEVELOP RES

The antiinflammatory activity of topically applied coal-derived fulvic acids (called oxifulvic acid) at 4.5% and 9% was compared with that of diclofene sodium at 1% and betamethasone at 0.1% in a murine model of contact hypersensitivity. Mice were sensitised with dinitrofluorobenzene and challenged 6 days later by application to the dorsal surface of the right ear. The inflamed ears of the mice were then treated topically, and the thickness of the ears was measured daily. Oxifulvic acid at both concentrations compared favourably with both diclofene sodium and betamethasone in suppressing the cutaneous inflammatory response. Oxifulvic acid possesses antiinflammatory properties and may be of clinical benefit in the treatment of inflammatory skin conditions in humans. Drug Dev. Res. 53:29–32, 2001. © 2001 Wiley-Liss, Inc.

Effect of Shilajit on Mouse Peritoneal Macrophages

Article

Nov 1993
PHYTOTHER RES

The effect of processed shilajit (SJ-P) was evaluated on murine peritoneal macrophages and on the cohabiting fibroblasts. The study revealed a dynamic aspect of modulation of the peritoneal cells by SJ-P (200–600 mcg/mouse), when administered intraperitoneally. The findings further suggested that by carefully determining the dose, SJ-P can be used in wound healing and in related inflammatory disease states.

Shilajitin Cancer Treatment: Probable Mode of Action

Abstract

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