Pharmacokinetics and Pharmacodynamics of Morroniside: A Review

Li, Bo; Lei, Shanshan; Xiong, Shanbai; Chen, Suhong; Zhang, Zhenqing

doi:10.1177/1934578x19856526

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…MR has been documented to possess anti-oxidation, antiinflammation, and anti-apoptosis properties (Gao et al, 2020;Deng et al, 2021;Park et al, 2021). It can exert a neuroprotective role in neurodegenerative diseases by eliminating ROS to enhance the total antioxidant capacity of the rat cortex, thereby preventing nerve cells from H 2 O 2 -induced oxidation injury (Wang et al, 2009;Yao et al, 2009;Zhang et al, 2017c;Li B et al, 2019). Likewise, MR has been proven to protect lung activity against aging by maintaining the cell proliferative state and normal cell morphology and inhibiting apoptosis (Chen et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

Zhou

Yao

et al. 2022

Front. Pharmacol.

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Intervertebral disc (IVD) degeneration (IVDD) which is highly prevalent within the elderly population, is a leading cause of chronic low back pain and disability. Nucleus pulposus (NP) cell senescence plays an indispensable role in the pathogenesis of IVDD. Morroniside is a major iridoid glycoside and one of the quality control metrics of Cornus officinalis Siebold & Zucc (CO). An increasing body of evidence suggests that morroniside and CO-containing formulae share many similar biological effects, including anti-inflammatory, anti-oxidative, and anti-apoptotic properties. In a previous study, we reported that Liuwei Dihuang Decoction, a CO-containing formula, is effective for treating IVDD by targeting p53 expression; however, the therapeutic role of morroniside on IVDD remains obscure. In this study, we assessed the pharmacological effects of morroniside on NP cell senescence and IVDD pathogenesis using a lumbar spine instability surgery-induced mouse IVDD model and an in vitro H 2 O 2 -induced NP cell senescence model. Our results demonstrated that morroniside administration could significantly ameliorate mouse IVDD progression, concomitant with substantial improvement in extracellular matrix metabolism and histological grading score. Importantly, in vivo and in vitro experiments revealed that morroniside could significantly reduce the increase in SA-β-gal activities and the expression of p53 and p21, which are the most widely used indicators of senescence. Mechanistically, morroniside suppressed ROS-induced aberrant activation of Hippo signaling by inhibiting Mst1/2 and Lats1/2 phosphorylation and reversing Yap/Taz reduction, whereas blockade of Hippo signaling by Yap/Taz inhibitor-1 or Yap/Taz siRNAs could antagonize the anti-senescence effect of morroniside on H 2 O 2 -induced NP cell senescence model by increasing p53 expression and activity. Moreover, the inhibition of Hippo signaling in the IVD tissues by morroniside was further verified in mouse IVDD model. Taken together, our findings suggest that

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Section: Discussionmentioning

confidence: 99%

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

Zhou

Yao

et al. 2022

Front. Pharmacol.

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“…Morroniside has been shown to exert many biological effects, such as anti-inflammatory, anti-apoptotic, anti-oxidant, cardioprotective and neuroprotective via several mechanisms and signaling pathways, i.e., STAT3, NF-κB, MAPK and PI3K/Akt pathways and molecules regulating the autophagic flux [ 184 , 185 , 186 , 187 , 188 , 189 ]. It has thus long been used to treat degenerative diseases of the nervous system, to inhibit platelet aggregation, to prevent diabetic angiopathies and renal damage, to treat OA and to reduce bone resorption [ 190 ].…”

Section: Plant-derived Compounds With a Reported Senotherapeutic Acti...mentioning

confidence: 99%

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Mavrogonatou,

Kletsas

2024

Metabolites

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Chronic low back pain, a major cause of disability with a great global socioeconomic impact, has been inextricably associated with intervertebral disc degeneration. On the other hand, an enhanced number of senescent cells has been identified in aged and degenerated intervertebral discs and their senescence-associated secretory phenotype (SASP) has been connected with qualitative/quantitative alterations in the extracellular matrix and ultimately with the disturbance of tissue homeostasis. Given that selective elimination of senescent cells (by the so-called senolytics) or amendment of their secretome towards a less catabolic/inflammatory phenotype (by molecules known as senomorphics) has been reported to alleviate symptoms of several age-associated diseases and to improve tissue quality during aging, here we will review the emerging role of senolytic and senomorphic agents derived from plants and natural products against intervertebral disc degeneration. The mode of action of these senotherapeutics, as well as the challenges in their practical application, will also be explicitly discussed in an attempt to direct their more targeted and effective use in exclusive or combinatorial therapeutic schemes for the prevention and/or treatment of disc degenerative disorders.

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“…Several studies have been conducted to determine the concentration of morroniside in biological matrices [9][10][11]. The absolute oral bioavailability of morroniside in rats was calculated to be only 3.6-7.0% [9,12]. The plasma levels of morroniside administered intravenously are much higher than those after oral administration.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the intestinal absorption of morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 cell monolayer model

Zhu

et al. 2020

PLoS ONE

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Morroniside is a biologically active polyphenol found in Cornus officinalis Sieb. et Zucc (CO) that exhibits a broad spectrum of pharmacological activities, such as protecting nerves, and preventing diabetic liver damage and renal damage. However, little data are available regarding the mechanism of its intestinal absorption. Here, an in vitro human intestinal epithelial cell model of cultured Caco-2 cells was applied to study the absorption and transport of morroniside. The effects of donor concentration, pH and inhibitors were investigated. The bidirectional permeability of morroniside from the apical (AP) to the basolateral (BL) side and in the reverse direction was studied. When administered at three tested concentrations (5, 25 and 100 μM), the apparent permeability coefficient (P app ) values in the AP-to-BL direction ranged from 1.59 × 10 −6 to 2.66 × 10 −6 cm/s. In the reverse direction, BL-to-AP, the value was ranged from 2.67 × 10 −6 to 4.10 × 10 −6 cm/s. The data indicated that morroniside transport was pH-dependent. The permeability of morroniside was affected by treatment with various inhibitors, such as multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. The mechanisms of the intestinal absorption of morroniside may involve multiple transport pathways, such as the passive diffusion and efflux protein-mediated active transport especially involving multidrug resistance protein 2 and breast cancer resistance protein. After the addition of CO, the P app values in the AP-to-BL direction increased significantly, therefore, it can be assumed that some ingredients in the CO promote morroniside absorption in the small intestine.

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Pharmacokinetics and Pharmacodynamics of Morroniside: A Review

Cited by 6 publications

References 32 publications

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Characterization of the intestinal absorption of morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 cell monolayer model

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