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Review ArticleExperimental Studies

The Guggul for Chronic Diseases: Ancient Medicine, Modern Targets

SHISHIR SHISHODIA, KUZHUVELIL B. HARIKUMAR, SUCHISMITA DASS, KRISHAN G. RAMAWAT and BHARAT B. AGGARWAL
Anticancer Research November 2008, 28 (6A) 3647-3664;
SHISHIR SHISHODIA
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KUZHUVELIL B. HARIKUMAR
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SUCHISMITA DASS
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KRISHAN G. RAMAWAT
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BHARAT B. AGGARWAL
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  • For correspondence: aggarwal@mdanderson.org
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Abstract

Identification of active principles and their molecular targets from traditional medicine is an enormous opportunity for modern drug development. Gum resin from Commiphora wightii (syn C. mukul) has been used for centuries in Ayurveda to treat internal tumors, obesity, liver disorders, malignant sores and ulcers, urinary complaints, intestinal worms, leucoderma (vitiligo), sinuses, edema and sudden paralytic seizures. Guggulsterone has been identified as one of the major active components of this gum resin. This steroid has been shown to bind to the farnesoid X receptor and modulate expression of proteins with antiapoptotic (IAP1, XIAP, Bfl-1/A1, Bcl-2, cFLIP, survivin), cell survival, cell proliferation (cyclin D1, c-Myc), angiogenic, and metastatic (MMP-9, COX-2, VEGF) activities in tumor cells. Guggulsterone mediates gene expression through regulation of various transcription factors, including NF-κ B, STAT-3 and C/EBPα, and various steroid receptors such as androgen receptor and glucocorticoid receptors. Modulation of gene expression by guggulsterone leads to inhibition of cell proliferation, induction of apoptosis, suppression of invasion and abrogation of angiogenesis. Evidence has been presented to suggest that guggulsterone can suppress tumor initiation, promotion and metastasis. This review describes the identification of molecular targets of guggulsterone, cellular responses to guggulsterone, and animal studies and clinical trials of guggulsterone in cancer and other diseases.

  • Guggul
  • guggulsterone
  • cancer
  • apoptosis
  • hyperlipidemia
  • inflammation
  • review

Footnotes

  • Abbreviations: ABC, ATP-binding cassette; ABCB1, ATP-binding cassette subfamily B; AP-1, activator protein-1; BSEP, bile salt export pump; CAR, constitutive androstane receptor; CDK, cyclin-dependent kinase; COX, cyclo-oxygenase; DSS, dextran sulfate sodium; EKG, electrocardiogram; ERK, extracellular signal-regulated kinase; FGF, fibroblast growth factor; FXR, farnesoid X receptor; HDL, high-density lipoprotein; HIV, human immunodeficiency virus; H2O2, hydrogen peroxide; HPLC, high-performance liquid chromatography; HPTLC, high-performance TLC; HUVEC, human umbilical vein endothelial cells; HVEC, human vascular endothelial cells; HVSMC, human vascular smooth muscle cells; IAP, inhibitor of apoptosis; I-BABP, ileum bile acid binding protein; IEC, intestinal epithelial cells; IFN-γ, interferon gamma; IκBα, inhibitory subunit of NF-κB; IL, interleukin; iNOS, inducible nitric oxide synthase; JAK, janus kinase; JNK, cJun N-terminal kinase; LDL, low-density lipoprotein; MAPK, mitogen-activated protein kinase; MKK4, MAP kinase kinase; MMP, matrix metalloproteinase; MRP1, multidrug-resistance protein 1; NF-κB, nuclear factor-κB; PARP, polyadenosine ribose polymerase; PBMC, peripheral blood mononuclear cells; PCNA, proliferating cell nuclear antigen; PGE, prostaglandin E; PMA, phorbol myristate acetate; PXR, pregnane X receptor; RANKL, receptor activator of NF-κB ligand; SCC, squamous cell carcinoma; SHP, small heterodimer partner; SMCS, S-methyl cysteine sulfoxide; STAT, signal transducer and activator of transcription; TGF, transforming growth factor; TLC, thin-layer chromatography; TNF, tumor necrosis factor; VDR, vitamin D receptor; VEGF, vascular endothelial growth factor; VLDL, very low-density lipoprotein; WOMAC, Western Ontario and McMaster Osteoarthritis Index.

  • Received May 22, 2008.
  • Revision received July 21, 2008.
  • Accepted September 5, 2008.
  • Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (6A)
Anticancer Research
Vol. 28, Issue 6A
November-December 2008
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The Guggul for Chronic Diseases: Ancient Medicine, Modern Targets
SHISHIR SHISHODIA, KUZHUVELIL B. HARIKUMAR, SUCHISMITA DASS, KRISHAN G. RAMAWAT, BHARAT B. AGGARWAL
Anticancer Research Nov 2008, 28 (6A) 3647-3664;

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The Guggul for Chronic Diseases: Ancient Medicine, Modern Targets
SHISHIR SHISHODIA, KUZHUVELIL B. HARIKUMAR, SUCHISMITA DASS, KRISHAN G. RAMAWAT, BHARAT B. AGGARWAL
Anticancer Research Nov 2008, 28 (6A) 3647-3664;
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