Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry

Ramakrishna, Rachumallu; Bhateria, Manisha; Singh, Rajbir; Puttrevu, Santosh Kumar; Bhatta, Rabi Sankar

doi:10.1016/j.jpba.2016.02.047

Cited by 18 publications

(12 citation statements)

References 21 publications

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“…After 21 days of AGN administration (Day 35), all rats were anesthetized with Nembutal, then abdominal aortic serum and synovial tissues were collected. The dosage, concentration, and intervention time of AGN are all referred to the previous study [19,20].…”

Section: Methodsmentioning

confidence: 99%

“…Subsequent studies explored the pharmaceutical components of "Sanse Powder" using ultraperformance liquid chromatography and identified agnuside (AGN), a nontoxic, natural small molecule isolated from the extract of Vitex negundo L. (Verbenaceae), as a part of medicinal effective ingredients [17]. Meanwhile, accumulating evidence has demonstrated the antioxidation, anti-inflammatory, analgesia, and many other properties of AGN as an iridoid glyco-side [18][19][20]. Nevertheless, the medicinal effects of AGN evaluated in existing studies are still very limited, nor are the targets of AGN's efficacy clear.…”

Section: Introductionmentioning

confidence: 99%

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Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1α and NLRP3 Inflammasome

Zhang

et al. 2021

Mediators of Inflammation

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Increasing evidence has shown that NLRP3 inflammasome activation participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last study also revealed the vital role of NLRP3 inflammasome, highly associated with tissue hypoxia, in the onset and development of knee osteoarthritis (KOA). In this study, we tried to find a possible benign intervention for that pathological process. Agnuside (AGN), a nontoxic, natural small molecule isolated from the extract of Vitex negundo L. (Verbenaceae), has been demonstrated to have antioxidation, anti-inflammatory, analgesia, and many other properties as an iridoid glycoside, although its specific target is still unclear. Therefore, we established MIA-induced KOA model rats and investigated the effects of AGN oral gavage on oxygen-containing state, NLRP3 inflammasome, synovitis, and fibrosis in KOA. Pimonidazole staining and HIF-1α immunohistochemical assay both showed that AGN at the oral dose of 6.25 mg/kg can effectively relieve local hypoxia in synovial tissue. Besides, we observed a decrease of HIF-1α, caspase-1, ASC, and NLRP3 after AGN intervention, both in the mRNA and protein levels. In addition, rats treated with the AGN showed less inflammatory reaction and fibrosis, not only in the expression of NLRP3, inflammasome downstream factors IL-1β and IL-18, and fibrosis markers TGF-β, TIMP1, and VEGF but also in the observation of HE staining, anatomical characteristics, Sirius Red staining, and type I collagen immunohistochemistry. Subsequently, we established LPS-induced models of fibroblast-like synoviocytes (FLSs) mimicking the inflammatory environment of KOA and activating NLRP3 inflammasome. FLSs treated with AGN (3 μM) resulted in a downregulation of HIF-1α and the components required for NLRP3 inflammasome activation. Meanwhile, the content of proinflammatory factors IL-1β and IL-18 in FLS supernatant was also reduced by AGN. In addition, both mRNA and protein levels of the fibrotic markers were significantly decreased after AGN management. To conclude, this study demonstrates that AGN alleviates synovitis and fibrosis in experimental KOA through the inhibition of HIF-1α accumulation and NLRP3 inflammasome activation. Additionally, not only does it reveal some novel targets for anti-inflammatory and antioxidant effects of AGN but also announces its potential value in treating KOA in humans.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1α and NLRP3 Inflammasome

Zhang

et al. 2021

Mediators of Inflammation

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“…On the other hand, the C max value of agnuside when injected intravenously (62,852.32 ± 16,013.94 ng/mL) was significantly higher than that of the oral administration. It is the highest in the intestine, which may be the reason for its low oral bioavailability, and it could be cleared out of all tissues within 8 h. Agnuside had the highest content in the intestine, followed by the kidney, indicated that it plays an important role in the extrahepatic clearance as the main excretory organ [118]. At present, there have been some studies on the pharmacokinetics of iridoids, but only limited to a few compounds, the pharmacokinetics of this class of compounds should be fully explored, and their metabolites and mechanisms should be comprehensively and systematically studied.…”

Section: Iridoid Glycosidesmentioning

confidence: 99%

“…At present, there have been some studies on the pharmacokinetics of iridoids, but only limited to a few compounds, the pharmacokinetics of this class of compounds should be fully explored, and their metabolites and mechanisms should be comprehensively and systematically studied. excretory organ [118]. At present, there have been some studies on the pharmacokinetics of iridoids, but only limited to a few compounds, the pharmacokinetics of this class of compounds should be fully explored, and their metabolites and mechanisms should be comprehensively and systematically studied.…”

Section: Iridoid Glycosidesmentioning

confidence: 99%

Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics

et al. 2020

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Iridoids are a class of active compounds that widely exist in the plant kingdom. In recent years, with advances in phytochemical research, many compounds with novel structure and outstanding activity have been identified. Iridoid compounds have been confirmed to mainly exist as the prototype and aglycone and Ι and II metabolites, by biological transformation. These metabolites have been shown to have neuroprotective, hepatoprotective, anti-inflammatory, antitumor, hypoglycemic, and hypolipidemic activities. This review summarizes the new structures and activities of iridoids identified locally and globally, and explains their pharmacokinetics from the aspects of absorption, distribution, metabolism, and excretion according to the differences in their structures, thus providing a theoretical basis for further rational development and utilization of iridoids and their metabolites.

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“…Four flavonoids, viz, agecorynin C, medicocarpin, 4 -O-methylglucoliquiritigenin, and 5,6,7,8,3 ,4 ,5 -heptamethoxyflavone, a crude drug, viz, zizybeoside I, and an O-glycosyl compound named benzyl gentiobioside (all with an m/z 415.15) were detected. 6-O-Methylarmillaridin (m/z 445.18), belonging to the family of melleolides and analogues, was detected to be present in the current study.An eremophilane-type sesquiterpene lactone, namely eremopetasitenin B2 (m/z 447.18)-an important biogenetic intermediate, and eremosulphoxinolide A-a terpene lactone (m/z 447.18), along with a terpenoid, viz, agnuside (m/z 449.15), an active constituent playing a role in the estrogenic activity for the potential treatment of premenstrual syndrome in women[34], were found to be present. Additionally, two anthocyanins malonylshisonin/4 -demalonylsalvianin (m/z 825 19).…”

mentioning

confidence: 99%

Non-Targeted Secondary Metabolite Profile Study for Deciphering the Cosmeceutical Potential of Red Marine Macro Alga Jania rubens—An LCMS-Based Approach

Dixit

Reddy

2017

Cosmetics

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This study aims to unveil the cosmeceutical traits of Jania rubens by highlighting its mineral composition, antioxidant potential, and presence of bioactive molecules using non-targeted metabolite profiling. This study showed that among minerals, (macro), Ca (14790.33 + 1.46 mg/100 g dry weight (DW)) and in (micro) Fe (84.93 + 0.89 mg/100 g DW) was the highest. A total of 23 putative metabolites in the +ESI (Electrospray Ionization) mode of LCMS-TOF (Liquid Chromatography Mass Spectrometry-Time of Flight) were detected. Two anthocyanins-malonylshisonin and 4-demalonylsalvianin (m/z 825.19; anti-aging, antioxidant, anticancer properties) were detected. Two flavonoids, viz, medicocarpin and agecorynin C, 4-O-methylglucoliquiritigenin-a flavonoid-7-O-glycoside, and 5,6,7,8,3 ,4 ,5-heptamethoxyflavone, a polymethoxygenated flavone (m/z 415.15), were detected. Maclurin 3-C-(2 ,3 ,6-trigalloylglucoside) (m/z 863.15) (antioxidant, antimicrobial and anticancer traits) and theaflavonin (m/z 919.18), belonging to the class of theaflavins (whitening and anti-wrinkle agent), were obtained. Pharmacologically active metabolites like berberrubin (m/z 305.1; antitumor activity), icaceine (m/z 358.24; anticonvulsant properties), agnuside (m/z 449.15; constituent for treatment of premenstrual syndrome), γ-coniceine (m/z 108.12; formulations to treat breast cancer), eremopetasitenin B2, and eremosulphoxinolide A (m/z 447.18; therapeutic effect of allergy and asthma) were observed. 6-O-Methylarmillaridin (m/z 445.18) (antimicrobial and antifungal) and simmondsin 2-ferulate, (m/z 534.21) (insecticidal, antifungal and antifeedant) were detected. Aromatic lignans, viz, 8-Acetoxy-4-methoxypinoresinol, sesartemin, and cubebinone (m/z 413.16), in addition to an aromatic terpene glycoside, tsangane L3 glucoside (m/z 357.23), were detected. Zizybeoside I, benzyl gentiobioside, and trichocarposide were also detected. The determination of antioxidant potential was performed through assays such as like DPPH (2,2-diphenyl-1-picrylhydrazyl), FRAP (Ferric Ion Reducing Antioxidant Power), ABTS (2,2-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid)), and total antioxidants. Therefore, this study progresses the probability for the inclusion of J. rubens as an ingredient in modern day cosmetic formulations.

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Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry

Cited by 18 publications

References 21 publications

Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1α and NLRP3 Inflammasome

Agnuside Alleviates Synovitis and Fibrosis in Knee Osteoarthritis through the Inhibition of HIF-1α and NLRP3 Inflammasome

Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics

Non-Targeted Secondary Metabolite Profile Study for Deciphering the Cosmeceutical Potential of Red Marine Macro Alga Jania rubens—An LCMS-Based Approach

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