+86-28-82633987
Synonym name:
Catalogue No.: BP0702
Cas No.: 19210-12-9
Formula: C24H30O11
Mol Weight: 494.493
Botanical Source: Melittis melissophyllum and Harpagophytum procumbens
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
Description:
Harpagoside has anti-inflammatory effects, it blocks lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model, and it does not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model, it may lead to a partial prevention of obesity-induced atherosclerosis by attenuating inflammatory responses. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-κB activation. Harpagoside exerts neuroprotection effect and ameliorates learning and memory deficit appears to be associated, at least in part, with up-regulation of brain-derived neurotrophic factor (BDNF) content as well as activating its downstream signaling pathways, e.g., MAPK/PI3K pathways.
References:
Cytokine, 2015, 76(2):368-74.
Inhibitory effects of harpagoside on TNF-α-induced pro-inflammatory adipokine expression through PPAR-γ activation in 3T3-L1 adipocytes.
Obesity is closely associated with increased production of pro-inflammatory adipokines, including interleukin (IL)-6, plasminogen activator inhibitor (PAI)-1, and adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, which contribute to chronic and low-grade inflammation in adipose tissue. Harpagoside, a major iridoid glycoside present in devil's claw, has been reported to show anti-inflammatory activities by suppression of lipopolysaccharide (LPS)-induced production of inflammatory cytokines in murine macrophages. The present study is aimed to investigate the effects of Harpagoside on both tumor necrosis factor (TNF)-α-induced inflammatory adipokine expression and its underlying signaling pathways in differentiated 3T3-L1 cells.
METHODS AND RESULTS:
Harpagoside significantly inhibited TNF-α-induced mRNA synthesis and protein production of the atherogenic adipokines including IL-6, PAI-1, and MCP-1. Further investigation of the molecular mechanism revealed that pretreatment with Harpagoside activated peroxisome proliferator-activated receptor (PPAR)-γ.
CONCLUSIONS:
These findings suggest that the clinical application of medicinal plants which contain Harpagoside may lead to a partial prevention of obesity-induced atherosclerosis by attenuating inflammatory responses.
J Ethnopharmacol. 2006 Mar 8;104(1-2):149-55.
Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-kappa B activation.
Preparations of Harpagophytum procumbens, known as devil's claw, are used as an adjunctive therapy for the treatment of pain and osteoarthritis. Pharmacological evaluations have proven the effectiveness of this herbal drug as an anti-inflammatory and analgesic agent.
METHODS AND RESULTS:
The present study has investigated the mechanism of action of Harpagoside, one of the major components of Harpagophytum procumbens, using human HepG2 hepatocarcinoma and RAW 264.7 macrophage cell lines. Harpagoside inhibited lipopolysaccharide-induced mRNA levels and protein expression of cyclooxygenase-2 and inducible nitric oxide in HepG2 cells. These inhibitions appeared to correlate with the suppression of NF-kappaB activation by Harpagoside, as pre-treating cells with Harpagoside blocked the translocation of NF-kappaB into the nuclear compartments and degradation of the inhibitory subunit IkappaB-alpha. Furthermore, Harpagoside dose-dependently inhibited LPS-stimulated NF-kappaB promoter activity in a gene reporter assay in RAW 264.7 cells, indicating that Harpagoside interfered with the activation of gene transcription.
CONCLUSIONS:
These results suggest that the inhibition of the expression of cyclooxygenase-2 and inducible nitric oxide by Harpagoside involves suppression of NF-kappaB activation, thereby inhibiting downstream inflammation and subsequent pain events.
J Nat Prod. 2015 Sep 25;78(9):2167-74.
Harpagoside Inhibits RANKL-Induced Osteoclastogenesis via Syk-Btk-PLCγ2-Ca(2+) Signaling Pathway and Prevents Inflammation-Mediated Bone Loss.
Harpagoside (HAR) is a natural compound isolated from Harpagophytum procumbens (devil's claw) that is reported to have anti-inflammatory effects; however, these effects have not been investigated in the context of bone development.
METHODS AND RESULTS:
The current study describes for the first time that HAR inhibits receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro and suppresses inflammation-induced bone loss in a mouse model.HAR also inhibited the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose-dependent manner as well as the activity of mature osteoclasts, including filamentous actin (F-actin) ring formation and bone matrix breakdown. This involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of Syk-Btk-PLCγ2-Ca(2+) in RANKL-dependent early signaling, as well as the activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which resulted in the down-regulation of various target genes. Consistent with these in vitro results, HAR blocked lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model. However, HAR did not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model.
CONCLUSIONS:
These results suggest that HAR is a valuable agent against inflammation-related bone disorders but not osteoporosis induced by hormonal abnormalities.
HPLC of Harpagoside
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
175.3700
.0140
.0140
2.4353
.5203
.3819
Low
64.9599
4.8636
Yes
No
No
No
No
No
0.0
Yes
Yes
Yes
Yes
Harpagoside (CAS No.: 19210-12-9) is an important natural product, mainly isolated from the plant Harpagophytum procumbens (commonly known as Devil's Claw). As a monosaccharide diterpene lactone, this compound has attracted widespread attention due to its remarkable anti-inflammatory, anticancer, and neuroprotective activities. In recent years, with advances in natural product pharmacology and molecular biology technologies, the biological activity and mechanism of habaoside have been deeply studied, demonstrating its potential application value in the prevention and treatment of various diseases. This paper aims to systematically review the chemical structure and physicochemical properties of habaoside, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to explore its clinical application prospects and future research directions.
Habaoside is a glycoside compound containing a diterpene lactone backbone, with the molecular formula C22H28O11 and molecular weight 494.4930. Its structural feature is that a cyclic diterpene lactone is connected to a glucose residue via a glycosidic bond, resulting in high polarity. In terms of physicochemical properties, the LogP value of haba-oside is 0.0140, indicating strong hydrophilicity. The TPSA (topological pole surface area) is 175.3700, indicating high molecular surface polarity, and water solubility of 2.4353, indicating good solubility in water. The blood-brain barrier has low permeability, indicating limited direct penetration of the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of habaoside cardiotoxicity. The Ames mutagenic test result was 0.0, indicating a low genotoxicity risk.
Habatoside mainly comes from the plant Harpagophytum procumbens, which is unique to southern Africa, commonly known as the Devil's Claw. The plant is named for its distinctive hook-shaped fruit, which has traditionally been used to treat symptoms such as rheumatoid arthritis, indigestion, and pain. Habaoside, as one of the main active components of this plant, is abundant in the roots.
The extraction method typically uses solvent extraction combined with chromatography separation technology. Common extraction solvents include ethanol, water, and their mixed solvent systems. The extraction steps generally include crushing plant roots, using reflux or ultrasonic-assisted extraction, followed by liquid-liquid partitioning, column chromatography (such as silica gel, C18 reversed column) for purification, and finally qualitative and quantitative analysis by high-performance liquid chromatography (HPLC). In recent years, green and efficient technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to habaoside extraction, improving extraction efficiency and purity.
The earliest attention to pharmacological effects of habaoside was its remarkable anti-inflammatory activity. In vitro experiments have shown that habaoside can effectively inhibit the activity of cyclooxygenases COX-1 and COX-2, reducing prostaglandin production and thus alleviating inflammatory responses. Meanwhile, habaoside significantly inhibits nitric oxide (NO) production and induced nitric oxide (NO) protein expression in macrophages and hepatocellular cancer cells HepG2 by lipopolysaccharides (LPS), reducing the release of inflammatory mediators. In animal models, habaoside demonstrated good anti-inflammatory and analgesic effects, especially showing potential in relieving rheumatoid arthritis and chronic inflammation-related pain.
Habaoside exhibits inhibitory effects on various cancer cell lines, especially in liver, colon, and breast cancer cells, showing cell proliferation inhibition and apoptosis-inducing activity. Its anti-cancer mechanism involves regulating cell cycle-related proteins, activating apoptotic signaling pathways, and suppressing the tumor-related inflammatory microenvironment. Habaoside can downregulate the expression of pro-cancer genes, inhibit the NF-κB signaling pathway, and reduce the release of pro-inflammatory cytokines, thereby suppressing tumor growth and metastasis.
Research on habaoside in the field of neuroprotection is increasing. It can effectively counteract neurotoxicity induced by β-amyloid peptide (Aβ) and reduce neurodegenerative changes. In vitro neural cell models show that habaoside inhibits nerve cell apoptosis by regulating the anti-apoptotic protein BCL2 and reducing the expression of activated caspase-3 (CASP3). Additionally, habaoside can activate the nuclear factor 2-related factor 2 (NRF2) signaling pathway, enhancing cellular antioxidant capacity and reducing oxidative stress damage. Its regulatory effect on acetylcholinesterase (ACHE) also suggests its potential application value in cognitive dysfunction.
The multi-target mechanism of habaoside is the basis for its multiple pharmacological activities. The main targets and their related signaling pathways include:
The synergistic regulation of these targets gives habaoside a wide range of biological effects, especially its therapeutic potential in inflammation, tumors, and neurodegenerative diseases.
The druggability parameters of habaoside indicate good safety and a low risk of toxic side effects. It has moderate molecular weight, high polarity, and good water solubility, but its low blood-brain barrier penetration limits its ability to act directly on the central nervous system. The hERG channel was inhibited negatively and the Ames test showed no mutagenicity, suggesting low risks of cardiotoxicity and genotoxicity, meeting safety standards.
Pharmacokinetics, habaoside is relatively effective orally and is absorbed stably in the body, but due to its strong polarity and poor blood-brain barrier permeability, it may require drug carriers or structural modifications to improve central nervous system bioavailability. Metabolic pathways mainly involve hepatic enzyme systems, and the activity and safety of these metabolites require further research. Systematic studies on in vivo distribution, half-life, and excretion characteristics are still lacking, and future pharmacokinetic studies should be strengthened to guide clinical application.
Based on the multiple pharmacological activities of habaoside, its clinical application prospects are broad. First, as a natural anti-inflammatory ingredient, habaoside can be used as an adjunct treatment for rheumatoid arthritis, chronic inflammation, and related pain, offering good safety and tolerability. Second, its anti-cancer potential offers new ideas for adjuvant therapy on tumors, especially in the treatment of solid tumors such as liver cancer. In addition, the neuroprotective effect of habaoside provides new therapeutic targets for neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Although its blood-brain barrier permeability is relatively low, strategies such as nanocarriers and structural optimization are expected to enhance the efficacy of central nervous system drugs.
Future research should focus on pharmacokinetic optimization, formulation development, and clinical trial validation of habaoside, especially its application in neurodegenerative diseases. At the same time, in-depth analysis of its multi-target synergistic mechanism will help promote the translation of habaoside into clinical drugs.
As a natural diterpene glycoside derived from Harpagophytum procumbens, habaoside demonstrates great medicinal potential due to its remarkable anti-inflammatory, anticancer, and neuroprotective activities. Its multi-target and multi-pathway mechanisms provide valuable examples for pharmacological research of natural products. Although there are still certain challenges in pharmacokinetics and clinical applications, with the advancement of modern drug development technologies, habaoside is expected to become an important candidate for treating inflammation, tumors, and neurodegenerative diseases. In the future, structural optimization, mechanism research, and clinical validation should be strengthened to promote its clinical translation and benefit patients.
Shenshuai
Wenjing
Hedandan
