Total alkaloid fraction of Leonurus japonicus Houtt. Promotes angiogenesis and wound healing through SRC/MEK/ERK signaling pathway

Shi, Xiaoqin; Chen, Gan; Tan, Jiaqi; Li, Zhuo; Chen, Si-Min; He, Jiahui; Zhang, Li; Xu, Hong‐Xi

doi:10.1016/j.jep.2022.115396

Cited by 15 publications

(10 citation statements)

References 46 publications

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“…[2] Moreover, total alkaloids including uracil (peak 6), hypoxanthine, leonurine (peak 25), choline, guanine, stachydrine (peak 4), and trigonelline (peak 2) in LJ had anti-angiogenesis and wound-healing effects in vivo and in vitro. [15] In our previous studies indicated that stachysoside A (peak 34) and acteoside (peak 36) were main two constituents in a macroporous adsorption resin with 30 % ethanol elution fraction from Lagopsis supina that possessed prominent PBCRBS in blood stasis model rats. [16] On the other hand, flavonoids, such as schaftoside (peak 28), [31] rutin (peak 32), [32] scutellarin (peak 38), [33] kaempferol-3-Orutinoside (peak 41), [34] Baicalein 7-O-D-glucoside (peak 44), [35] Baicalin (peak 45), [36] and alkaloids (leonurine, peak 25; and stachydrine, peak 4), [2] as well as terpenoids (leoheterin, galeopsin, hispanone, 14trien-7-one, leojaponoins E and F) [2] showed antiinflammatory activities.…”

Section: Discussionmentioning

confidence: 93%

“…On the one hand, alkaloids, including leonurine (peak 25), stachydrine (peak 4), trigonelline (peak 2), and chloride, and terpenoids ((2 S ,5 S )‐2‐hydroxy‐2,6,10,10‐tetramethyl‐1‐oxaspiro‐[4,5]dec‐6‐en‐8‐one, prehispanolone, (−)‐(3 R ,5 S ,7 R ,8 R ,9 R ,10 S ,13 R ,15 R )‐3‐acetoxy‐7‐hydroxy‐15‐ethoxy‐9,13;15,16‐diepoxylabdan‐6‐one, (−)‐(5 S ,7 R ,8 R ,9 R ,10 S ,13 R ,15 R )‐7‐hydroxy‐15‐ethoxy‐9,13;15,16‐diepoxylabdan‐6‐one, and leonuketal), and steroids (β‐sitosterone and 24R‐5α‐stigmast‐3,6‐dione), along with phenylpropanoids (isogosferal and murrayone) exerted activating blood circulation effects [2] . Moreover, total alkaloids including uracil (peak 6), hypoxanthine, leonurine (peak 25), choline, guanine, stachydrine (peak 4), and trigonelline (peak 2) in LJ had anti‐angiogenesis and wound‐healing effects in vivo and in vitro [15] . In our previous studies indicated that stachysoside A (peak 34) and acteoside (peak 36) were main two constituents in a macroporous adsorption resin with 30 % ethanol elution fraction from Lagopsis supina that possessed prominent PBCRBS in blood stasis model rats [16] .…”

Section: Methodsmentioning

confidence: 99%

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Activating Blood Circulation, Anti‐Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling

Zhang

Nie

Yang

et al. 2023

Chemistry & Biodiversity

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Leonurus japonicus Houtt. has been traditionally used to treat many ailments. This study evaluated the activating blood circulation, anti-inflammatory, and diuretic effects of L. japonicus extract (LJ) and identified its phytochemicals. In this work, the phytochemicals in LJ were identified using liquid chromatography mass spectrometry. Rats were randomly assigned to three groups (n = 8): Control group was treated with saline, while the Model group (saline) and LJ group (426 mg/kg) had induced traumatic injury. All rats were treated with once by daily oral gavage for one week. The biochemical indices and protein expression were measured. Herein, 79 constituents were identified in LJ, which were effective in elevating body weight, food consumption, water intake, and urinary excretion volume, as well as in ameliorating traumatic muscle tissues in model rats. In addition, LJ prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen, thromboxane B2 (TXB2), TXB2/6-ketoprostaglandin F1α (6-keto-PGF1α), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tissue-type PA (t-PA), and PAI-1/u-PA, while significantly increasing antithrombin III, 6-keto-PGF1α, and t-PA contents. Furthermore, LJ notably inhibited tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, angiotensin II, antidiuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3 levels, and markedly elevating IL-10 and natriuretic peptide levels. Finally, LJ markedly reduced the protein expression of AQP1, AQP2, and AQP3 compared to the model group. Collectively, LJ possessed prominent activating blood circulation, antiinflammatory, and diuretic effects, thus supporting the clinical application of L. japonicus.

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Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Activating Blood Circulation, Anti‐Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling

Zhang

Nie

Yang

et al. 2023

Chemistry & Biodiversity

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“…38,39 Alkaloids also play a role in SRC/MEK/ERK signaling pathway regulation that promotes the wound healing process. 40…”

Section: Resultsmentioning

confidence: 99%

Wound healing activity and flavonoid contents of purslane (Portulaca grandiflora) of various varieties

et al. 2023

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“…CGF contains a large amount of EGF, and the binding of EGF to EGFR will lead to the activation of the downstream MEK/ERK pathway involved in the regulation of cell proliferation and metastasis [ 39 , 40 ]. Furthermore, the pharmacological mechanism of some drugs for wound healing is associated with the activation of the MEK/ERK pathway [ 41 , 42 ]. In particular, Yang et al reported that plant extracts promoted wound healing of anal fistula by activating the MEK/ERK pathway [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Autologous Bioactive Compound Concentrated Growth Factor Ameliorates Fistula Healing of Anal Fistula in a Pig Model and Promotes Proliferation and Migration of Human Skin Fibroblasts via Regulating the MEK/ERK Pathway

Zhang

Qiu

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Recent evidence suggested that autologous concentrated growth factor (CGF), a new bioactive compound from autologous blood is used widely as an ingenious biomaterial in tissue regeneration with anti-inflammatory properties. This study investigated whether CGF could be involved in the treatment of fistula healing in the anal fistula. For this purpose, the porcine anal fistula model was conducted using the rubber band ligation method and collected pig autogenic CGF to treat the fistulas. CGF treatment promoted fistula healing, which was reflected in the downregulation of inflammatory factors, upregulation of growth factors, and promoted epithelial-mesenchymal transition with increased collagen synthesis. Besides, 16S rRNA gene sequencing analysis of fistula tissues between the control and CGF groups showed that the microbial populations exhibiting significant differences were VadinCA02, Blastomonas, Deinococcus, Devosia, Sphingomonas, Rubrobacteria, and GW_34. CGF of volunteers were collected to process small interfering RNA- (siRNA-) ERK or siRNA-negative control transfected human skin fibroblasts (HSF). The results showed that CGF also promoted the proliferation and extracellular matrix-related functions in HSF, as well as activated the MEK/ERK pathway in vitro and in vivo. Finally, knockdown ERK reversed the effects of CGF in promoting wound healing in HSF. Collectively, our results suggest that the CGF as the bioactive compound from autologous blood exhibited great potential for repairing fistulas as well as promoting the proliferation and migration of human skin fibroblasts by triggering MEK/ERK signaling. These findings provided a fresh perspective for understanding the role of CGF in the management of fistulas.

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Total alkaloid fraction of Leonurus japonicus Houtt. Promotes angiogenesis and wound healing through SRC/MEK/ERK signaling pathway

Cited by 15 publications

References 46 publications

Activating Blood Circulation, Anti‐Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling

Activating Blood Circulation, Anti‐Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling

Wound healing activity and flavonoid contents of purslane (Portulaca grandiflora) of various varieties

Autologous Bioactive Compound Concentrated Growth Factor Ameliorates Fistula Healing of Anal Fistula in a Pig Model and Promotes Proliferation and Migration of Human Skin Fibroblasts via Regulating the MEK/ERK Pathway

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