Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation

Hsieh, Ming Jer; Liu, Hsien Ta; Wang, Chao Nin; Huang, Hsiu Yun; Lin, Yuling; Ko, Yu Shien; Wang, Jong Shyan; Chang, Vincent H.S.; Pang, Jong Hwei S.

doi:10.1007/s00109-016-1488-y

Cited by 66 publications

(144 citation statements)

References 41 publications

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“…BPC 157 reduces high myeloperoxidase (MPO) activity in colonic tissue (Veljaca et al., ), and in particular, heals fistulas (Baric et al., ; Grgic et al., ; Klicek et al., ), rescues failed anastomosis healing (Klicek et al., ; Sever et al., ; Vuksic et al., ), and markedly improves intestinal adaptation following massive bowel resection (Sever et al., ). Studies have shown different molecular mechanisms involved in BPC 157 beneficiary effects (Chang et al., , ; Hsieh et al., ; Huang et al., ). Thus, recently the increased expression and internalization of VEGFR2, and the activation of the VEGFR2‐Akt‐eNOS signaling pathway have been implicated (Hsieh et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown different molecular mechanisms involved in BPC 157 beneficiary effects (Chang et al, 2011(Chang et al, , 2014Hsieh et al, 2017;Huang et al, 2015). Thus, recently the increased expression and internalization of VEGFR2, and the activation of the VEGFR2-Akt-eNOS signaling pathway have been implicated (Hsieh et al, 2017). However, further studies will be needed to designate these effects to the affected honeybee midgut.…”

Section: Discussionmentioning

confidence: 99%

“…Thereby, BPC 157 exerts endothelium and mucosal protection in stomach, counteracts variously induced gastrointestinal lesions in different species (Duzel et al., ; Sikiric et al., , , , ), but has not been tested in social insects. Several molecular pathways are discussed as possible targets of BPC 157 (Cesarec et al., ; Chang, Tsai, Hsu, & Pang, ; Chang, Tsai, Lin, Hsu, & Pang, ; Hsieh et al., ; Huang et al., ; Tkalcevic et al., ). Thereby, BPC 157 was considered to be suitable for the extension of the beneficial effect to the entire gastrointestinal tract (Seiwerth et al.…”

Section: Introductionmentioning

confidence: 99%

“…Thereby, BPC 157 exerts endothelium and mucosal protection in stomach, counteracts variously induced | 615 TLAK GAJGER ET AL. gastrointestinal lesions in different species (Duzel et al, 2017;Sikiric et al, 2010Sikiric et al, , 2012Sikiric et al, , 2014Sikiric et al, , 2017, but has not been tested in social insects. Several molecular pathways are discussed as possible targets of BPC 157 (Cesarec et al, 2012;Chang, Tsai, Hsu, & Pang, 2014;Chang, Tsai, Lin, Hsu, & Pang, 2011;Hsieh et al, 2017;Huang et al, 2015;Tkalcevic et al, 2007). Thereby, BPC 157 was considered to be suitable for the extension of the beneficial effect to the entire gastrointestinal tract Sikiric et al, 2010Sikiric et al, , 2012Sikiric et al, , 2014Sikiric et al, , 2017Sikiric et al, 2011Sikiric et al, , 2013Sikiric et al, , 2016Duzel et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

Gajger

Ribarić²,

Skerl

et al. 2018

Vet Pharm & Therapeutics

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Nosema ceranae can cause major problems, such as immune suppression, gut epithelial cell degeneration, reduced honeybee lifespan, or suddenly colony collapse. As a novel approach in therapy, we hypothesize the stable gastric pentadecapeptide BPC 157 in honeybee therapy, to control N. ceranae invasions in apiary conditions: BPC 157 treated sugar syrup (0.25 L sugar syrup supplemented with 0.1 μg/ml BPC 157), as well as the pure sugar syrup (0.25 L sugar syrup; control), was administered to honeybee colonies in feeders situated under the roof of the hives, during 21 consecutive days, at the end of beekeeping season. The strength of honeybee colonies was increased 20 and 30 days after initial feeding with BPC 157 supplement (Day 1, 36.100 ± 698; Day 20, 64.860 ± 468; Day 30, 53.214 ± 312 estimated number of honeybees), in field conditions. The similar successful outcome occurs with the N. ceranae spore loads counted in the homogenates of sampled adult honeybees (Day 1, 6.286 ± 2.336; Day 20, 3.753 ± 1.835; Day 30, 2.005 ± 1.534 million spores/bee). Accordingly, with the noted increased strength of the colonies fed with sugar syrup supplemented with BPC 157, the number of N. ceranae spores per honeybee gradually decreased as well. Besides, honeybees infected with N. ceranae fed with sugar syrup exhibited severe damage of midgut wall layers and epithelial cells. By contrast, in honeybees infected with N. ceranae fed with sugar syrup supplemented with BPC 157, all damages were markedly attenuated, damages of the outer muscular coat, in particular. In conclusion, the results of the first field trial on diseased honeybee colonies with BPC 157 indicate significant therapeutic effects with the used oral therapy with BPC 157 supplementation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

Gajger

Ribarić²,

Skerl

et al. 2018

Vet Pharm & Therapeutics

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“…In a study conducted by Hsieh et al (2017), the authors aimed to explore the proangiogenic and therapeutic effect of BPC 157. Demonstrated by chick chorioallantoic membrane (CAM) and endothelial tube formation assays, both in vivo and in vitro, BPC 157 was shown to increase both vessel density and accelerate the recovery of blood flow in ischemic muscle, indicating a promotional effect on angiogenesis.…”

Section: Prolonged Therapeutic Benefitsmentioning

confidence: 99%

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

2019

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There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation.

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The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats

et al. 2020

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Background and purpose We focused on the, yet undescribed, therapy effect of the stable gastric pentadecapeptide BPC 157 in hippocampal ischemia/reperfusion injuries, after bilateral clamping of the common carotid arteries in rats. The background is the proven therapy effect of BPC 157 in ischemia/reperfusion injuries in different tissues. Furthermore, there is the subsequent oxidative stress counteraction, particularly when given during reperfusion. The recovering effect it has on occluded vessels, results with activation of the alternative pathways, bypassing the occlusion in deep vein thrombosis. Finally, the BPC 157 therapy benefits with its proposed role as a novel mediator of Roberts’ cytoprotection and bidirectional effects in the gut‐brain axis. Materials and Methods Male Wistar rats underwent bilateral clamping of the common carotid arteries for a 20‐min period. At 30 s thereafter, we applied medication (BPC 157 10 µg/kg; or saline) as a 1 ml bath directly to the operated area, that is, trigonum caroticum. We documented, in reperfusion, the resolution of the neuronal damages sustained in the brain, resolution of the damages reflected in memory, locomotion, and coordination disturbances, with the presentation of the particular genes expression in hippocampal tissues. Results In the operated rats, at 24 and 72 hr of the reperfusion, the therapy counteracted both early and delayed neural hippocampal damage, achieving full functional recovery (Morris water maze test, inclined beam‐walking test, lateral push test). mRNA expression studies at 1 and 24 hr, provided strongly elevated ( Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3, and Nos1 ) and decreased ( Nos2, Nfkb ) gene expression ( Mapk1 not activated), as a way how BPC 157 may act. Conclusion Together, these findings suggest that these beneficial BPC 157 effects may provide a novel therapeutic solution for stroke.

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Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation

Cited by 66 publications

References 41 publications

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats

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