Oxidised derivatives of silybin and their antiradical and antioxidant activity

Gažák, Radek; Svobodová, Alena Rajnochová; Psotová, Jitka; Sedmera, Petr; Přikrylová, Věra; Walterová, Daniela; Křen, Vladimı́r

doi:10.1016/j.bmc.2004.07.064

Cited by 140 publications

(72 citation statements)

References 32 publications

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“…15 Silibinin showed high solubility in PEG 400 (304.92 mg/mL), probably because of the ability of silibinin to form hydrogen bonds with polyethylene oxide moieties. Similarly, Cremophor composed of polyethylene oxide provided high solubilization to silibinin.…”

Section: Discussionmentioning

confidence: 99%

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

Chen

Chang

Shih

et al. 2015

IJN

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Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery.

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Section: Discussionmentioning

confidence: 99%

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

Chen

Chang

Shih

et al. 2015

IJN

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“…Therefore, some preparations have been made in recent years to improve the solubility and bioavailability of silybin, including phospholipid complexes [28] , sodium cholate/phospholipid complexes and povidone-sodium cholate-phospholipid mixed micelles [29,30] . Recently, 2,3-dehydrosilybin, an oxidized form of silybin, has been reported to exhibit a significantly greater antioxidant and anticancer activity in comparison with silybin [22] . We synthesized dehydrosilymarin following the method originally designed for the preparation of dehydrosilybin and confirmed that dehydrosilymarin showed increased antiradical and antioxidative capacities than those of silybin, dehydrosilybin and silymarin [5] .…”

Section: Discussionmentioning

confidence: 99%

“…Dehydrosilymarin was prepared essentially according to a reported method [22] , which was originally designed for the preparation of dehydrosilybin. In brief, silymarin was dissolved in pyridine and heated to 90 °C under reflux for 77 h with stirring.…”

Section: Synthesis Of Dehydrosilymarinmentioning

confidence: 99%

Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo

Chu

Tong

et al. 2011

Acta Pharmacol Sin

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Aim: To formulate proliposomes with a polyphase dispersed system composed of soybean phospholipids, cholesterol, isopropyl myristate and sodium cholate to improve the oral bioavailability of dehydrosilymarin, an oxidized form of herbal drug silymarin. Methods: Dehydrosilymarin was synthesized from air oxidation of silymarin in the presence of pyridine, and proliposomes were prepared by a film dispersion-freeze drying method. Morphological characterization of proliposomes was observed using a transmission electron microscope. Particle size and encapsulation efficiency of proliposomes were measured. The in vitro release of dehydrosilymarin from suspension and proliposomes was evaluated. The oral bioavailability of dehydrosilymarin suspension and proliposomes was investigated in rabbits. Results: The proliposomes prepared under the optimum conditions were spherical and smooth with a mean particle size in the range of 7 to 50 nm. Encapsulation efficiency was 81.59%±0.24%. The in vitro accumulative release percent of dehydrosilymarinloaded proliposomes was stable, which was slow in pH 1.2, and increased continuously in pH 6.8, and finally reached 86.41% at 12 h. After oral administration in rabbits, the relative bioavailability of proliposomes versus suspension in rabbits was 228.85%. Conclusion: Proliposomes may be a useful vehicle for oral delivery of dehydrosilymarin, a drug poorly soluble in water.

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“…Various studies also indicate that silymarin exhibits cancer preventive and anticarcinogenic effects (Zi et al 1998;Bhatia et al 1999). Silymarin has been shown to have diverse effects such as a potent antioxidant, anti-inflammatory, and antifibrinogenic (Gupta et al 2000;Lieber et al 2003;Gazák et al 2004). In this study, busulfan and bone marrow suppression were used as tools to reveal the silymarin-inhibiting effect against suppressing cell death of any extent.…”

Section: Introductionmentioning

confidence: 89%

Hematological and bone marrow parameters in busulfan-treated rats: effects of silymarin extract

2015

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Busulfan is an alkylating agent that can be used in the treatment and control of chronic myeloblastic leukemia. Milk thistle seed extract of dried herb in 1 to 4 % silymarin is a powerful antioxidant flavonoid. In this study, busulfan and bone marrow suppression were used to assess whether the effect of silymarin can suppress cell death, or at least reduce it. Fortytwo Wistar male rats were fed with a standard diet, divided into six groups of eight rats and treated as follows. Group 1-control group (received nothing). Group 2-control silymarin, 175 mg/kg/day silymarin was gavage for 14 days. Group 3-anemic control group, 20 mg/kg/day busulfan was injected intraperitoneally (i.p.) for 14 days. Group 4-experimental group 1 received 20 mg/kg/day busulfan (i.p.) for 14 days, and after 2 weeks, 175 mg/kg/day silymarin was gavage for 14 days. Group 5-two groups received 20 mg/kg/day dose busulfan (i.p.) for 14 days, and after 2 weeks, 250 mg/kg/day silymarin was gavage for 14 days. Group 6-three groups received 20 mg/kg/day dose busulfan (i.p.) for 14 days, and after 2 weeks, 325 mg/kg/day silymarin was gavage for 14 days. Hematological and bone marrow parameters were measured using standard routine procedures. The results showed that after 2 weeks, in the group that had received busulfan with healthy controls, leukocyte parameters were influenced more by the drug similar to the control group. In samples of bone marrow cells after treatment with silymarin, a slight difference between the groups was observed, but the cells are promyelocyte, myelocyte, and metamyelocyte, and band width in the control group of healthy controls and patient groups treated with silymarin was different. Decrease in bone marrow cells of control group was significantly different from the control group treated with silymarin. The effects of silymarin on bone marrow cells and peripheral blood leukocytes lead to reduced cell death, reducing oxidative stress and protecting cells against apoptosis, and the mechanisms, probably due to antioxidant properties, are unknown.

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Oxidised derivatives of silybin and their antiradical and antioxidant activity

Cited by 140 publications

References 32 publications

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo

Hematological and bone marrow parameters in busulfan-treated rats: effects of silymarin extract

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