Sikiric Predrag, Seiwerth Sven, Skrtic Anita, Staresinic Mario, Strbe Sanja, Vuksic Antonia, Sikiric Suncana, Bekic Dinko, Soldo Dragan, Grizelj Boris, Novosel Luka, Beketic Oreskovic Lidija, Oreskovic Ivana, Stupnisek Mirjana, Boban Blagaic Alenka, Dobric Ivan
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2025 Jun 19;18(6):928. doi: 10.3390/ph18060928.
Although approached through many concepts, the pleiotropic healing issue, specifically, maintaining/reestablishing tissue integrity, remains a central challenge in pharmacology, particularly when the process is misdirected or not properly controlled. Robert and Szabo's concept of cytoprotection holds that innate cell (epithelial (Robert), endothelial (Szabo)) integrity and protection/maintenance/reestablishment in the stomach is translated to other organ therapy (cytoprotection → organoprotection) via the cytoprotection agent's effect. Therefore, we defend stable gastric pentadecapeptide BPC 157 therapy's efficacy and pleiotropic beneficial effects, along with its high safety (LD1 not achieved), against speculation of its negative impact, speculation of angiogenesis toward tumorigenesis, increased NO and eNOS, damaging free radical formation, and neurodegenerative diseases (Parkinson's disease and Alzheimer's disease). Contrarily, in wound healing and general healing capabilities, as reviewed, as a cytoprotective agent and native cytoprotection mediator, BPC 157 controls angiogenesis and the NO-system's healing functions and counteracts the pathological presentation of neurodegenerative diseases in acknowledged animal models (i.e., Parkinson's disease and Alzheimer's disease), and it presents prominent anti-tumor potential in vivo and in vitro. BPC 157 resolved cornea transparency maintenance, cornea healing "angiogenic privilege" (vs. angiogenesis/neovascularization/tumorigenesis), and it does not produce corneal neovascularization but rather opposes it. Per Folkman's concept, it demonstrates an anti-tumor effect in vivo and in vitro. BPC 157 exhibits a distinctive effect on the NO-level (increase vs. decrease), always combined with the counteraction of free radical formation, and, in mice and rats, BPC 157 therapy counteracts Parkinson's disease-like and Alzheimer's disease-like disturbances. Thus, BPC 157 therapy means targeting angiogenesis and NO's cytotoxic and damaging actions but maintaining, promoting, or recovering their essential protective functions.
尽管通过多种概念来探讨,但多效性愈合问题,尤其是维持/重建组织完整性,仍然是药理学中的核心挑战,特别是当这个过程出现偏差或未得到适当控制时。罗伯特(Robert)和萨博(Szabo)的细胞保护概念认为,胃中固有细胞(上皮细胞(罗伯特)、内皮细胞(萨博))的完整性以及保护/维持/重建功能可通过细胞保护剂的作用转化为其他器官的治疗(细胞保护→器官保护)。因此,我们捍卫稳定的胃十五肽BPC 157疗法的疗效、多效性有益作用及其高安全性(未达到半数致死量),以应对关于其负面影响、对肿瘤发生的血管生成推测、一氧化氮(NO)和内皮型一氧化氮合酶(eNOS)增加、有害自由基形成以及神经退行性疾病(帕金森病和阿尔茨海默病)的猜测。相反,如所综述那样,在伤口愈合和一般愈合能力方面,作为一种细胞保护剂和天然细胞保护介质,BPC 157控制血管生成和NO系统的愈合功能,并在公认的动物模型(即帕金森病和阿尔茨海默病)中对抗神经退行性疾病的病理表现,并且它在体内和体外均呈现出显著的抗肿瘤潜力。BPC 157解决了角膜透明度维持、角膜愈合的“血管生成特权”(相对于血管生成/新生血管形成/肿瘤发生)问题,并且它不会产生角膜新生血管,而是起到对抗作用。根据福克曼(Folkman)的概念,它在体内和体外均表现出抗肿瘤作用。BPC 157对NO水平具有独特影响(升高或降低),始终伴随着对自由基形成的对抗作用,并且在小鼠和大鼠中,BPC 157疗法可对抗帕金森病样和阿尔茨海默病样紊乱。因此BPC 157疗法意味着针对血管生成以及NO的细胞毒性和破坏作用,但维持、促进或恢复其基本保护功能。