Addition of β-Lactoglobulin Produces Water-Soluble Shikonin

Albreht, Alen; Vovk, Irena; Simonovska, Breda

doi:10.1021/jf303153d

Cited by 20 publications

(25 citation statements)

References 46 publications

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“…Unfortunately, studies on the toxicity of this molecule in different species and with different administration routes are still missing and should be carried out. Due to its high lipophilicity, shikonin is generally used in creams and ointments, that is, oil-based preparations; indeed, its insolubility in water is usually the cause of its low bioavailability [3]. Moreover, shikonin and its derivatives are also thermolabile and prone to oxidation and polymerization [3][4][5].…”

Section: The Pharmacokinetics and Bioavailability Of Shikoninmentioning

confidence: 99%

“…Due to its high lipophilicity, shikonin is generally used in creams and ointments, that is, oil-based preparations; indeed, its insolubility in water is usually the cause of its low bioavailability [3]. Moreover, shikonin and its derivatives are also thermolabile and prone to oxidation and polymerization [3][4][5]. One study using 3 H-shikonin in mice showed that shikonin was rapidly absorbed after oral and intramuscular administration, with a half-life in plasma of 8.79 h and a distribution volume of 8.91 L/kg.…”

Section: The Pharmacokinetics and Bioavailability Of Shikoninmentioning

confidence: 99%

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Pharmacological Properties of Shikonin – A Review of Literature since 2002

et al. 2013

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!The naphthoquinone shikonin is the main active principle of Zicao, a traditional Chinese herbal medicine made from the dried root of Lithospermum erythrorhizon. Studies carried out over the past 30 years have provided a scientific basis for the use of Zicao which has been long employed in folk medicine to treat a variety of inflammatory and infectious diseases. In particular, shikonin has been shown to possess many diverse properties, including antioxidant, anti-inflammatory, antithrombotic, antimicrobial, and wound healing effects. The fact that shikonin shows so many beneficial properties has increased the interest in this molecule dramatically, especially in the past few years. The aim of this review is to provide an update of the new data published on shikonin, whose wide spectrum of pharmacological effects as well as pharmacokinetic properties and toxicity make it a highly interesting target molecule.

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Section: The Pharmacokinetics and Bioavailability Of Shikoninmentioning

confidence: 99%

Section: The Pharmacokinetics and Bioavailability Of Shikoninmentioning

confidence: 99%

Pharmacological Properties of Shikonin – A Review of Literature since 2002

et al. 2013

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“…We suppose that the reaction mechanism could be based on nucleophilic addition, where thiol of Cys121 or Cys119 attacks the electrophilic ethylidene C3-C3' bond of PCB with formation of a thioether bond, similarly to formation of thioether between BLG Cys121 and shikonin (Albreht, et al, 2012). According to all obtained results, we hypothesize that initially there is fast formation of non-covalent BLG-PCB complexes, with PCB binding preferentially in the calyx.…”

Section: Molecular Docking Reveals the Binding Of Pcb In The Calyx Ofmentioning

confidence: 61%

“…were identified (Albreht, Vovk, & Simonovska, 2012). Therefore, SMD simulation was used to simulate disulfide interchange between Cys121 and Cys119.…”

Section: Molecular Docking Reveals the Binding Of Pcb In The Calyx Ofmentioning

confidence: 99%

Covalent binding of food-derived blue pigment phycocyanobilin to bovine β-lactoglobulin under physiological conditions

et al. 2018

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In this study, we investigated structural aspects of covalent binding of food derived blue pigment phycocyanobilin (PCB) to bovine β-lactoglobulin (BLG), major whey protein, by spectroscopic, electrophoretic, mass spectrometry and computational methods. At physiological pH (7.2), we found that covalent pigment binding via free cysteine residue is slow (k = 0.065 min), of moderate affinity (K = 4 × 10 M), and stereo-selective. Binding also occurs at a broad pH range and under simulated gastrointestinal conditions. Adduct formation rises with pH, and in concentrated urea (k = 0.101 min). The BLG-PCB adduct has slightly altered secondary and tertiary protein structure, and bound PCB has higher fluorescence and more stretched conformation than free chromophore. Combination of steered molecular dynamic for disulfide exchange, non-covalent and covalent docking, favours Cys119 residue in protein calyx as target for covalent BLG-PCB adduct formation. Our results suggest that this adduct can serve as delivery system of bioactive PCB.

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“…However, the therapeutic efficacy of shikonin is somewhat limited due to poor aqueous solubility and extensive first-pass metabolism, which are similar to those of many other chemotherapeutic drugs. 15,16 Thus, designing new formulations, which can obviously increase shikonin solubility and decrease its toxicity to normal tissue, is highly desired in clinics.…”

Section: Introductionmentioning

confidence: 99%

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

Su¹,

Huang²,

Chen³

et al. 2017

IJN

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The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intratumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy.

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Addition of β-Lactoglobulin Produces Water-Soluble Shikonin

Cited by 20 publications

References 46 publications

Pharmacological Properties of Shikonin – A Review of Literature since 2002

Pharmacological Properties of Shikonin – A Review of Literature since 2002

Covalent binding of food-derived blue pigment phycocyanobilin to bovine β-lactoglobulin under physiological conditions

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

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