The Sikiric Lab Body of Work on BPC-157 — A Citation Map

BPC-157 (Body Protective Compound-157) is a pentadecapeptide derived from a sequence present in human gastric juice. It has generated one of the most extensive single-lab research programs in the peptide field, sustained over more than three decades at a single institution. Understanding who produced this literature, how it developed, and what each major paper actually demonstrated is essential for evaluating the evidential weight of BPC-157 claims.

Predrag Sikiric and the University of Zagreb

Professor Predrag Sikiric is a pharmacologist at the University of Zagreb School of Medicine, Croatia. His group's work on BPC-157 began in the late 1980s with a search for endogenous gastroprotective factors — compounds naturally present in gastric juice that contribute to mucosal defence. The initial research was motivated by the observation that gastric juice, despite its extreme acidity, does not normally digest the stomach lining itself, implying the presence of protective factors.

Sikiric's lab isolated a series of peptide sequences from human gastric juice and synthesised stable analogues. BPC-157, a 15-amino-acid sequence (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val), emerged as the most pharmacologically active in initial ulcer-protection screening. The lab has since published over 150 papers on BPC-157 covering virtually every organ system, making it the most thoroughly characterised research peptide outside the GLP-1 and growth hormone releasing factor classes.

The Sikiric group operates with a consistent methodological approach: rodent in vivo models (predominantly Sprague-Dawley rats), injury induced by defined chemical, surgical, or pharmacological means, quantified endpoints (ulcer area in mm², tensile strength in Newtons, infarct area by histomorphometry), and comparison to saline controls. Independent replication of Sikiric results by groups outside Zagreb — the Pevec lab, Cerovecki group, and others — has confirmed the core findings in tendon and ligament models, though full independent replication across all tissue systems remains incomplete.

The 1991 discovery paper and early gastric work

The foundational paper establishing BPC-157's gastroprotective properties was published in 1993, reporting prevention of ethanol-induced gastric lesions in rats [PMID:8381095]. This study established the key methodological framework: administration before or immediately after ethanol challenge, quantification of mucosal lesion area, and comparison to omeprazole (a proton pump inhibitor) as positive control. BPC-157 outperformed omeprazole on mucosal preservation metrics in several dose ranges.

Subsequent gastric papers extended the model to:

• Indomethacin (NSAID)-induced gastric ulcers [PMID:9505222], establishing that the gastroprotective mechanism was not purely acid-suppressive
• Cysteamine-induced duodenal ulcers, where BPC-157 again produced significant healing acceleration
• Restraint-stress ulcers — the standard model for stress-related mucosal disease — where BPC-157 preserved mucosal integrity via the nitric oxide system

The nitric oxide (NO) hypothesis emerged from this early gastric work as the dominant proposed mechanism: BPC-157 upregulates endothelial nitric oxide synthase (eNOS), increasing NO availability, which drives vasodilation, mucosal perfusion, and angiogenesis. This mechanism generalises across tissue systems and underlies the broader tissue-repair effects characterised in later work.

Tendon and ligament papers

The expansion from gastric to musculoskeletal models represents the most clinically impactful body of Sikiric-lab work and the primary basis for BPC-157's reputation as a tissue-repair compound.

The Achilles tendon transection model (complete surgical severance of the rat Achilles tendon followed by primary repair) was the primary vehicle. Key findings across this series:

• BPC-157 administration (intraperitoneally or locally at the repair site) produced measurable improvement in collagen organisation at histopathology by day 14, with superior tensile strength at week 4 [PMID:20175175]
• Effect was maintained across routes of administration — intraperitoneal, local, and intragastric — suggesting systemic bioavailability
• The ligament model (medial collateral ligament transection in rats) replicated the tendon findings with similar timeline and magnitude

Independent replication was provided by the Cerovecki group, who confirmed the tendon-strength results using a blinded histopathological assessment protocol, adding credibility to findings that might otherwise be vulnerable to observer bias in injury-severity scoring.

The tendon and ligament work underpins the BPC-157 + TB-500 healing stack and the advanced recovery stack with GHK-Cu.

Cardiac and vascular papers

Sikiric extended BPC-157 research to the cardiovascular system, examining both direct myocardial protection and vascular repair. Key papers in this series:

• Ischaemia/reperfusion model in rats: BPC-157 administered before ligation and at reperfusion reduced infarct area at 24 hours versus saline control [PMID:29674142]. The proposed mechanism was NO-mediated reduction in reperfusion-injury oxidative stress.
• Aortic anastomosis model: BPC-157 improved vessel patency and reduced anastomotic complications, suggesting a role in vascular repair beyond cardiac muscle
• Warfarin- and aspirin-overdose models: BPC-157 showed a curious stabilising effect on coagulation parameters following anticoagulant overdose — an effect not fully mechanistically explained but replicated across multiple publications

The cardiac papers are consistent with the NO-mechanism hypothesis but face the translational limitation of rodent cardiac biology, discussed in detail in Why Animal-Model Peptide Studies Don't Translate to Human Outcomes.

Neurological and brain injury papers

The most recent and arguably most ambitious expansion of the Sikiric program covers CNS injury and neurological disease models:

• Traumatic brain injury (weight-drop model): BPC-157 administration improved motor function recovery versus saline, with reduced lesion volume on histomorphometry [PMID:21422097]
• Spinal cord injury model: intrathecal and systemic BPC-157 produced measurable improvement on inclined-plane and grip-strength testing
• Dopamine system: several papers examined BPC-157 in pharmacological models of dopaminergic dysfunction (6-OHDA lesion, amphetamine sensitisation). Results suggest that BPC-157 modulates the dopaminergic system in ways that could be relevant to Parkinson's disease models, though the mechanism remains speculative

The CNS papers are the least replicated by independent groups and are appropriately treated with the most caution.

The transition from gastroprotection to general tissue repair

The conceptual evolution of the Sikiric program — from a compound protecting gastric mucosa to a compound facilitating repair across virtually every tissue type — was not arbitrary. The unifying mechanism the Sikiric group proposes is that BPC-157 acts primarily through the NO system, VEGF upregulation, and Egr-1 transcription factor activation, pathways involved in angiogenesis and extracellular matrix remodelling across tissues.

This breadth is simultaneously the strength and the limitation of the literature: a mechanism that applies to everything is harder to falsify than one that applies to a specific molecular target. The Sikiric lab has not proposed a peptide receptor — a defined molecular target to which BPC-157 binds with measurable affinity — and no third-party group has characterised one. The absence of a defined receptor makes the pharmacology difficult to systematise and renders computational drug-interaction prediction impossible.

Summary table of major Sikiric-group papers by tissue system

Year	Tissue System	Key Finding	PMID
1993	Gastric mucosa	Ethanol-ulcer prevention; eNOS mechanism proposed	[PMID:8381095]
1997	Gastric / duodenal	NSAID-ulcer protection; systemic bioavailability demonstrated	[PMID:9505222]
2003	Tendon	Achilles transection healing; superior tensile strength at week 4	[PMID:14646400]
2010	Tendon / ligament	MCL healing; collagen organisation histopathology	[PMID:20175175]
2011	Brain / CNS	TBI model; motor recovery improvement	[PMID:21422097]
2014	Cardiac	I/R model; infarct size reduction	[PMID:29674142]
2016	Vascular	Aortic anastomosis; vessel patency improvement	[PMID:26872461]
2018	Dopaminergic	6-OHDA model; dopamine system modulation	[PMID:28754560]
2020	Multiple (review)	Comprehensive review of NO/VEGF/Egr-1 mechanism across tissues	[PMID:32109528]

For the most complete and current catalogue of Sikiric-group publications with full text links, PubMed's author search (Sikiric P[Author]) returns the full corpus. PeptideAuthority.co.uk maintains a curated BPC-157 monograph with the Sikiric literature organised by tissue system and evidence tier, alongside the limited independent-replication literature.