Bioavailability Challenges Associated with Development of Saponins As Therapeutic and Chemopreventive Agents

Gao, Song; Basu, Sumit; Yang, Zhen; Deb, Arijita; Hu, Ming

doi:10.2174/138945012804545498

Cited by 57 publications

(50 citation statements)

References 108 publications

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“…Different formulations of OA, such as freeze-dried polyvinylpyrrolidone and sodium caprate OA, increased dissolution rate and intestinal permeability when tested in vitro in Caco-2 cells and in vivo in Sprague-Dawley rats, respectively [130,131]. Pharmacokinetic parameters of OA and other pentacyclic triterpene saponins have been reported in detail including the metabolism of OA [132]. Cao et al [133] synthetized numerous water-soluble amino acid analogues of OA and tested for their bioavailability.…”

Section: Preclinical and Clinical Pharmacokinetic Studies Of Oa Anmentioning

confidence: 99%

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

et al. 2014

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Oleanolic acid (OA, 3β-hydroxyolean-12-en-28-oic acid) is a ubiquitous pentacyclic multifunctional triterpenoid, widely found in several dietary and medicinal plants. Natural and synthetic OA derivatives can modulate multiple signaling pathways including nuclear factor-κB, AKT, signal transducer and activator of transcription 3, mammalian target of rapamycin, caspases, intercellular adhesion molecule 1, vascular endothelial growth factor, and poly (ADP-ribose) polymerase in a variety of tumor cells. Importantly, synthetic derivative of OA, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), and its C-28 methyl ester (CDDO-Me) and C28 imidazole (CDDO-Im) have demonstrated potent antiangiogenic and antitumor activities in rodent cancer models. These agents are presently under evaluation in phase I studies in cancer patients. This review summarizes the diverse molecular targets of OA and its derivatives and also provides clear evidence on their promising potential in preclinical and clinical situations.

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Section: Preclinical and Clinical Pharmacokinetic Studies Of Oa Anmentioning

confidence: 99%

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

et al. 2014

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“…35,36 Poor bioavailability has been the major challenge in developing hydrophilic saponins as clinically useful drugs. In this study, an SNEDDS based on phospholipid complex technique was designed to improve the oral bioavailability of ASD.…”

Section: Discussionmentioning

confidence: 99%

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex

Shen¹,

Bi²,

Tian³

et al. 2016

IJN

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Background Akebia saponin D (ASD) exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS) based on the drug–phospholipid complex technique was developed to improve the oral absorption of ASD. Methods ASD–phospholipid complex (APC) was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats. Results The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in n -octanol. Peceol (Glyceryl monooleate [type 40]), Cremophor ® EL (Polyoxyl 35 castor oil), and Transcutol HP (Diethylene glycol monoethyl ether) were selected as oil, surfactant, and cosurfactant, respectively. The optimal formulation was composed of Glyceryl monooleate (type 40), Polyoxyl 35 castor oil, Diethylene glycol monoethyl ether, and APC (1:4.5:4.5:1.74, w/w/w/w), which showed a particle size of 148.0±2.7 nm and a zeta potential of −13.7±0.92 mV after dilution with distilled water at a ratio of 1:100 (w/w) and good colloidal stability. Pharmacokinetic studies showed that APC-SNEDDS exhibited a significantly greater C max 1 (733.4±203.8 ng/mL) than ASD (437.2±174.2 ng/mL), and a greater C max 2 (985.8±366.6 ng/mL) than ASD (180.5±75.1 ng/mL) and APC (549.7±113.5 ng/mL). Compared with ASD, T max 1 and T max 2 were both remarkably shortened by APC-SNEDDS. The oral bioavailability in rats was enhanced significantly to 183.8% and 431.8% by APC and APC-SNEDDS, respectively. Conclusion These results indicated that APC-SNEDDS was a promising drug delivery system to enhance the oral bioavailability of ASD.

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“…However, using crude plant powder as material to make a formulation is unreasonable because plant material could increase the variability during formulation. In addition, the active components are difficult to be absorbed directly from plant material because only soluble substrates can be absorbed in the intestine (Gao et al, 2012). In this study, an active fraction GS409 was afforded from ZSP by fractionation which was guided by the MTT assay (Section “extraction and isolation”).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is unusual to use crude plant material to make the tablet directly because plant material could increase the variability during formulation. Moreover, the active components are difficult to be absorbed directly from plant material because only soluble substrates can be absorbed in the intestine (Gao et al, 2012). The aim of this study is to extract ZSP tablets to afford a more potential fraction and establish a reasonable quality control based on the activity and the absorption of major components.…”

Section: Introductionmentioning

confidence: 99%

Developing an activity and absorption-based quality control platform for Chinese traditional medicine: Application to Zeng-Sheng-Ping(Antitumor B)

Yin

Yang

et al. 2015

Journal of Ethnopharmacology

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Ethnopharmacological relevance Zeng-Sheng-Ping (ZSP) is a marketed Chinese traditional medicine used for cancer prevention. Aim of the study Currently, for the quality control of Chinese traditional medicines, marker compounds are not selected based on bioactivities and pharmaceutical behaviors in most of the cases. Therefore, even if the “quality” of the medicine is controlled, the pharmacological effect could still be inconsistent. The aim of this study is to establish an activity and absorption-based platform to select marker compound(s) for the quality control of Chinese traditional medicines. Materials and methods We used ZSP as a reference Chinese traditional medicine to establish the platform. Activity guided fractionation approach was used to purify the major components from ZSP. NMR and MS spectra were used to elucidate the structure of the isolated compounds. MTT assay against oral carcinoma cell line (SCC2095) was performed to evaluate the activities. UPLC-MS/MS was used to quantify the pure compounds in ZSP and the active fraction. The permeabilities of the identified compounds were evaluated in the Caco-2 cell culture model. The intracellular accumulation of the isolated compounds was evaluated in the SCC2095 cells. Results The major compounds were identified from ZSP. The contents, anti-proliferation activities, permeabilities, and intracellular accumulations of these compounds were also evaluated. The structure of these purified compounds were identified by comparing the NMR and MS data with those of references as rutaevine (1), limonin (2) , evodol (3), obacunone (4), fraxinellone (5), dictamnine (6), maackiain (7), trifolirhizin (8), and matrine (9). The IC50 of compounds 5, 6, and 7 against SCC2095 cells were significantly lower than that of ZSP. The uptake permeability of compounds 5, 6, and 7 were 2.58 ± 0. 3 × 10−5, 4.33 ± 0.5 × 10−5, and 4.27 ± 0.8 × 10−5 respectively in the Caco-2 cell culture model. The intracellular concentrations of these compounds showed that compounds 5, 6, and 7 were significantly accumulated inside the cells. Conclusion Based on the activity against oral carcinoma cell line as well as the absorption permeability, compound 5, 6, and 7 are selected as quality control markers for ZSP. A activity and absorption-based platform was established and successfully used for the quality control of ZSP.

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Bioavailability Challenges Associated with Development of Saponins As Therapeutic and Chemopreventive Agents

Cited by 57 publications

References 108 publications

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex

Developing an activity and absorption-based quality control platform for Chinese traditional medicine: Application to Zeng-Sheng-Ping(Antitumor B)

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Bioavailability Challenges Associated with Development of Saponins As Therapeutic and Chemopreventive Agents

Cited by 57 publications

References 108 publications

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D&ndash;phospholipid complex

Developing an activity and absorption-based quality control platform for Chinese traditional medicine: Application to Zeng-Sheng-Ping(Antitumor B)

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Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex