Naturally occurring compound
Multiple targets including antioxidant enzymes, inflammatory mediators, cancer cell signaling pathways, and neuroprotective pathways. Gigantol exhibits antioxidant activity by scavenging free radicals and upregulating antioxidant enzymes. It has anti-inflammatory effects by inhibiting the production of pro-inflammatory mediators such as NO, TNF-α, and IL-6. The compound shows anticancer activity by inducing apoptosis, inhibiting cell proliferation, and modulating signaling pathways. Neuroprotective effects have been observed, with the compound protecting neurons from oxidative stress and excitotoxicity. Hepatoprotective effects are attributed to its antioxidant and anti-inflammatory activities.

Gigantol has demonstrated significant in vitro anticancer activity against multiple cancer cell lines. In lung cancer cells, gigantol induces ferroptosis by specifically interacting with SLC7A11 (solute carrier family 7 member 11), a subunit of the cystine/glutamate antiporter system Xc⁻, leading to inhibition of glutathione synthesis and disruption of redox homeostasis. This results in reduced cysteine uptake, decreased GPX4 activity, and subsequent ferroptotic cell death. Gigantol also suppresses cancer stem cell-like phenotypes in lung cancer cells at non-toxic concentrations, significantly reducing anchorage-independent growth, tumor spheroid formation, and the expression of stem cell markers CD133 and ALDH1A1 by suppressing Akt activation and decreasing pluripotency factors Oct4 and Nanog. In addition, gigantol exhibits anti-inflammatory properties by reducing pro-inflammatory markers and arachidonic acid metabolites through NF-κB, AKT, PI3K, and JNK/cPLA2/12-LOX pathways. Molecular docking studies identified MMP-13 as a promising target with a binding affinity of -8.8 kcal/mol. Gigantol also binds to and inhibits aldose reductase, with a half-maximal inhibitory concentration of 0.05845 mM, contributing to its anticataract activity.

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Research indicates that Gigantol possesses several potential biological properties:
Anti-inflammatory: Inhibits inflammatory responses by modulating signaling pathways such as NF-κB.
Antioxidant: Scavenges free radicals and reduces oxidative stress.
Antitumor: Demonstrates pro-apoptotic, anti-migratory, and anti-invasive effects in models of lung cancer, liver cancer, etc.
Neuroprotective: Shows potential in protecting against neurodegenerative diseases like Parkinson's and Alzheimer's.
Antimicrobial & Antiviral: Exhibits inhibitory effects against certain bacteria and viruses.
Others: Also reported to have anti-diabetic, anti-osteoporotic, and other activities.

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Gigantol exhibits antioxidant activity by scavenging free radicals and reducing oxidative stress. The compound has anti-inflammatory effects, inhibiting the production of pro-inflammatory mediators in activated immune cells. Anticancer activity has been demonstrated, with the compound inducing apoptosis and inhibiting proliferation in various cancer cell lines. Neuroprotective effects have been observed, with the compound protecting neurons from damage. Hepatoprotective effects have been reported. The compound's specific in vitro activities would depend on the concentrations tested and the assay systems used.

Gigantol exhibits significant in vivo pharmacological activities. In lung cancer xenograft models, gigantol demonstrates anti-lung cancer efficacy through the induction of ferroptosis via the SLC7A11-GPX4 axis. Pharmacokinetic studies in mice revealed that gigantol shows rapid absorption, exhibits non-linear kinetic profile, and distributes with high concentrations in the liver and lungs. In a study using Kunming mice, oral administration of gigantol at 10 mg/kg showed significant tissue distribution in the liver and lungs, with RNA sequencing indicating enrichment of PPAR signaling pathways, and gigantol was identified as a dual PPARα/γ agonist. Gigantol also ameliorates CCl₄-induced liver injury by preventing activation of the JNK/cPLA2/12-LOX inflammatory pathway. Furthermore, gigantol exerts protective effects against diabetic cataracts in streptozotocin-induced rat models.

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In vivo studies of gigantol have demonstrated its antioxidant, anti-inflammatory, neuroprotective, and hepatoprotective effects in animal models. The compound has been shown to reduce inflammation, protect against oxidative stress, and improve neurological function. Its anticancer activity has been evaluated in tumor xenograft models. Dendrobium species, from which gigantol is derived, have been used in traditional medicine for their health-promoting properties. Further studies are needed to fully characterize the compound's pharmacokinetic and pharmacodynamic properties.

Non-cell-based assays for gigantol include standard antioxidant assays such as DPPH radical scavenging, ABTS radical scavenging, and FRAP assays. Anti-inflammatory activity is assessed by measuring inhibition of COX-2, LOX, or cytokine production in enzyme assays. Anticancer activity is assessed by cell viability assays using cancer cell lines. Standard analytical methods including HPLC, NMR, and mass spectrometry are used for compound characterization.

Cell-based assays for gigantol use various cell lines to assess its biological activities. Macrophage cell lines (e.g., RAW 264.7) are stimulated with LPS and treated with the compound, and inflammatory mediators in culture supernatant are measured. Cancer cell lines are treated with the compound, and cell viability (MTT), apoptosis (Annexin V/PI), and cell cycle progression are assessed. For neuroprotective studies, neuronal cell lines are exposed to oxidative stress inducers and treated with the compound, and cell viability and neurite outgrowth are measured. Hepatoprotective effects are assessed in hepatocyte cell lines.

In vivo studies of gigantol have been conducted in animal models. For anti-inflammatory studies, carrageenan-induced paw edema models are used. For neuroprotective studies, models of cerebral ischemia or neurodegeneration are used. For anticancer studies, tumor xenograft models are used. For hepatoprotective studies, CCl₄- or APAP-induced liver injury models are used. The compound is administered orally, intraperitoneally, or intravenously. Relevant endpoints are measured.

Gigantol exhibits favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Pharmacokinetic studies in mice have shown that gigantol is rapidly absorbed after oral administration, with a non-linear kinetic profile. Tissue distribution studies demonstrate that gigantol accumulates primarily in the liver and lungs, with high concentrations detected in these organs. The compound undergoes phase II metabolism as a major metabolic pathway. ADMET analysis has confirmed gigantol's compatibility with necessary physicochemical, pharmacokinetic, and toxicity properties, supporting its potential as a drug candidate. However, limited oral bioavailability remains a challenge that requires further investigation.

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Pharmacokinetic data for gigantol are limited. As a bibenzyl compound with a molecular weight of approximately 274.31 g/mol, it is expected to have moderate lipophilicity and oral bioavailability. The compound is soluble in organic solvents such as DMSO and ethanol. It should be stored as a powder at -20°C for up to 3 years or in solvent at -80°C for 1 year. It is intended for research use only.

Gigantol demonstrates a favorable safety profile in preclinical studies. Acute toxicity tests showed no toxic reaction in mice treated with gigantol-containing formulations. In ocular toxicity studies, no eye irritation or skin irritation was observed in rabbit eyes and skin following single-dose and multiple-dose administrations, and no allergic reactions were detected in guinea pigs. Gigantol at non-toxic concentrations effectively suppressed cancer stem cell-like phenotypes without causing significant cytotoxicity to normal cells. No adverse effects were found on THP-1-derived macrophages in in vitro studies. ADMET analysis has confirmed the compound's compatibility with necessary toxicity properties, further supporting its safety profile. However, comprehensive toxicological data, including long-term toxicity studies, remain to be fully established.

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Specific toxicity data for gigantol are limited. As a naturally occurring bibenzyl, it is generally considered to have low toxicity. However, comprehensive toxicological studies have not been reported. Standard laboratory safety practices should be followed when handling this compound, including the use of personal protective equipment. It is intended for research use only.

[1]. A substituted 1,2-diarylethane from Cymbidium giganteum. Phytochemistry. 1985 Feb 5;24(2): 321-4.

According to reports, 3',4-dihydroxy-3,5'-dimethoxybibenzyl has been found in Dendrobium nobile, Dendrobium chrysanthum, and other organisms with available data.

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Gigantol is a bibenzyl compound found in various orchid species, including Dendrobium giganteum and other Dendrobium species. Dendrobium has been used in traditional Chinese medicine for its health-promoting properties, including its effects on immune function, vision, and longevity. Gigantol exhibits various biological activities including antioxidant, anti-inflammatory, anticancer, neuroprotective, and hepatoprotective effects. It is used as a reference standard for the identification and quantification of bibenzyl compounds in plant extracts and for research purposes. It is for research use only.

C16H18O4

274.31

274.121

83088-28-2

67884-30-4

10221179

Colorless to light yellow Oil

2.9

2

4

5

20

284

0

OC1C=C(CCC2C=C(OC)C(O)=CC=2)C=C(OC)C=1

BMSPEISBKGSBTR-UHFFFAOYSA-N

InChI=1S/C16H18O4/c1-19-14-8-12(7-13(17)10-14)4-3-11-5-6-15(18)16(9-11)20-2/h5-10,17-18H,3-4H2,1-2H3

4-[2-(3-hydroxy-5-methoxyphenyl)ethyl]-2-methoxyphenol

Gigantol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 50 mg/mL (182.28 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)