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Verbascoside (Acteoside; Kusaginin; TJC-160), a natural product isolated from Lantana camara, is novel and potent inhibitor of the Oligomerization of Pneumolysin. It acts as an ATP-competitive inhibitor of PKC, with an IC50 of 25 µM, with antitumor, anti-inflammatory and antineuropathic pain activity.
Physicochemical Properties
| Molecular Formula | C29H36O15 |
| Molecular Weight | 624.5872 |
| Exact Mass | 624.205 |
| Elemental Analysis | C, 55.77; H, 5.81; O, 38.42 |
| CAS # | 61276-17-3 |
| PubChem CID | 5281800 |
| Appearance | White to yellow solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 908.8±65.0 °C at 760 mmHg |
| Flash Point | 294.7±27.8 °C |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C |
| Index of Refraction | 1.689 |
| LogP | 2.44 |
| Hydrogen Bond Donor Count | 9 |
| Hydrogen Bond Acceptor Count | 15 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 44 |
| Complexity | 936 |
| Defined Atom Stereocenter Count | 10 |
| SMILES | C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)O[C@@H]2[C@H]([C@@H](O[C@@H]([C@H]2OC(=O)/C=C/C3=CC(=C(C=C3)O)O)CO)OCCC4=CC(=C(C=C4)O)O)O)O)O)O |
| InChi Key | FBSKJMQYURKNSU-ZLSOWSIRSA-N |
| InChi Code | InChI=1S/C29H36O15/c1-13-22(36)23(37)24(38)29(41-13)44-27-25(39)28(40-9-8-15-3-6-17(32)19(34)11-15)42-20(12-30)26(27)43-21(35)7-4-14-2-5-16(31)18(33)10-14/h2-7,10-11,13,20,22-34,36-39H,8-9,12H2,1H3/b7-4+/t13-,20+,22-,23+,24+,25+,26+,27+,28+,29-/m0/s1 |
| Chemical Name | [(2R,3R,4R,5R,6R)-6-[2-(3,4-Dihydroxyphenyl)ethoxy]-5-hydroxy-2-(hydroxymethyl)-4-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate |
| Synonyms | Kusaginin; TJC-160; TJC 160; TJC160; Acetoside; 61276-17-3; Verbacoside; NSC 603831; Kusaginin |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | PKC (IC50 = 25 μM) |
| ln Vitro | Verbascoside has an IC50 of 25 μM and is an ATP competitive PKC inhibitor. In terms of ATP and histones, verbascoside has a Kis of 22 and 28 μM, respectively. Verbascoside, with an IC50 of 13 μM, exhibits strong anti-tumor action against L-1210 cells[1]. Verbascoside (5, 10 μM) prevents T cell costimulators CD86 and CD54, pro-inflammatory cytokines, and NFκB pathways from being activated in THP-1 cells by 2,4-dinitrochlorobenzene (DNCB) [2]. |
| ln Vivo |
In a mouse model of 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD), verbascoside (1%) decreases the incidence of overall scratching behavior and the severity of skin lesions. In DNCB-induced skin damage, verbascoside also inhibits the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-4 mRNA [2]. Intraperitoneally administered verbascoside (50, 100 mg/kg) does not alleviate cold allodynia resulting from chronic compression injury (CCI). On day three, verbascoside (200 mg/kg, intraperitoneally) decreased the rats' hypersensitivity to cold-stimulated acetone. Verbascoside also considerably lessened the behavioral alterations linked to neuropathy. Verbascoside also raises Bcl-2 and decreases Bax on day three [3]. Researchers examined the effects of verbascoside in rats subjected to chronic constriction injury (CCI). Verbascoside (50, 100, and 200 mg/kg, i.p.), was administered from the day of surgery for 14 days. Spinal cord levels of apoptotic factors and glia markers were quantified on days 3, 7, and 14 post-CCI. Oxidative stress markers were assessed on days 7 and 14. CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post-CCI. A significant increase in the levels of Iba (a marker of microglia activation) and Bax (a proapoptotic factor) was observed on day 3. Iba remained high on day 7. In contrast, there were no differences in glial fibrillary acidic protein contents between sham and CCI animals. Malondialdehyde increased and reduced glutathione decreased on day 14. Verbascoside significantly attenuated behavioral changes associated with neuropathy. Bax decreased, while Bcl-2 was increased by verbascoside on day 3. Verbascoside also reduced Iba protein on days 3 and 7. The results support evidence that microglial activation, apoptotic factors, and oxidative stress may have a pivotal role in the neuropathic pain pathogenesis. It is suggested that antinociceptive effects elicited by verbascoside might be through the inhibition of microglia activation, apoptotic pathways, and antioxidant properties. [3] |
| Enzyme Assay | Verbascoside [1] isolated from Lantana camara is an inhibitor of protein kinase C (PKC) from the rat brain. Half-maximal inhibition of the kinase occurs at 25 microM. Verbascoside interacted with the catalytic domain of PKC and was a competitive inhibitor with respect to ATP (Ki = 22 microM) and a non-competitive inhibitor with respect to the phosphate acceptor (histone IIIS). This effect was further evidenced by the fact that verbascoside inhibited native PKC and its catalytic fragment identically and did not affect [3H]-phorbol-12,13-dibutyrate binding to PKC. The antitumor activity of verbascoside measured in vitro might be due at least in part to inhibition of PKC. [1] |
| Animal Protocol |
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the interplay between multiple genetic and environmental factors. The pathogenesis of AD remains incompletely understood. Treatment with topical steroids for chronic AD symptoms has severe side effects and so a new treatment is required. Verbascoside is a hydrophilic phenylethanoid glycoside with antioxidant, anti-inflammatory properties.
Methods: Verbascoside was evaluated in AD-like lesions induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. Overall symptomatic score and serological and molecular changes of the skin lesions were investigated. Results: Verbascoside relieved the overall AD-like symptoms such as scratching behavior and skin lesion severity. At whole-body level, verbascoside significantly reduced DNCB-induced IgE and Th2 cytokines in the peripheral blood. At the skin lesion site, verbascoside also inhibited DNCB-induced production of proinflammatory cytokine TNF-α, IL-6, and IL-4 mRNA. In a human monocyte THP-1 model, verbascoside could suppress DNCB-induced upregulation of CD86 and CD54 at the cell surface, the secretion of the proinflammatory cytokines TNF-α and IL-6, and the activation of NFκB signaling in a dose-dependent manner. Conclusion: Our results demonstrate that verbascoside could be a potential therapeutic agent for the treatment of AD. [2] |
| Toxicity/Toxicokinetics |
5281800 rat LD50 oral >5 gm/kg Farmaco, Edizione Scientifica., 35(3), 1980 5281800 rat LD50 intraperitoneal >5 gm/kg Farmaco, Edizione Scientifica., 35(3), 1980 5281800 mouse LD50 oral >5 gm/kg Farmaco, Edizione Scientifica., 35(3), 1980 5281800 mouse LD50 intraperitoneal >5 gm/kg Farmaco, Edizione Scientifica., 35(3), 1980 |
| References |
[1]. Verbascoside isolated from Lantana camara, an inhibitor of protein kinase C. J Nat Prod. 1991 Nov-Dec;54(6):1595-600. [2]. Verbascoside Alleviates Atopic Dermatitis-Like Symptoms in Mice via Its Potent Anti-Inflammatory Effect. Int Arch Allergy Immunol. 2018;175(4):220-230. [3]. The Effect of Verbascoside in Neuropathic Pain Induced by Chronic Constriction Injury in Rats. Phytother Res. 2016 Jan;30(1):128-35. |
| Additional Infomation |
Acteoside is a glycoside that is the alpha-L-rhamnosyl-(1->3)-beta-D-glucoside of hydroxytyrosol in which the hydroxy group at position 4 of the glucopyranosyl moiety has undergone esterification by formal condensation with trans-caffeic acid. It has a role as a neuroprotective agent, an antileishmanial agent, an anti-inflammatory agent, a plant metabolite and an antibacterial agent. It is a cinnamate ester, a disaccharide derivative, a member of catechols, a polyphenol and a glycoside. It is functionally related to a hydroxytyrosol and a trans-caffeic acid. Acteoside is under investigation in clinical trial NCT02662283 (Validity and Security of Reh-acteoside Therapy for Patients of IgA Nephropathy). Acteoside has been reported in Acanthus ilicifolius, Acanthus ebracteatus, and other organisms with data available. See also: Harpagophytum zeyheri root (part of). |
Solubility Data
| Solubility (In Vitro) |
H2O : ≥ 100 mg/mL (~160.11 mM) DMSO : ≥ 100 mg/mL (~160.11 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6011 mL | 8.0053 mL | 16.0105 mL | |
| 5 mM | 0.3202 mL | 1.6011 mL | 3.2021 mL | |
| 10 mM | 0.1601 mL | 0.8005 mL | 1.6011 mL |