Long-term gastric acid suppression has been associated with complications in mucosa integrity. But the roles for gastric acid in extragastral damage manifestation have not been reported. We examined the effects of acid suppression on oesophageal and oral mucosa (OM). Previously we showed that an extract of Cucurbita maxim sweet seed (eCSE) plays an important role in non-erosive lesions (NEOL) in proximal part of GI tract. The present study was designed to study effects of eCSE on oesophageal mucosa (OEM) and OM under modification of enterosalivary nitrites recirculation (mESNR). The study was done on rats subdivided to the first group (control) injected with vehicle at a dose 1 ml, i.p.; the second group of animals was subdivided into three subgroups and rats were sacrificed after administration of R (Ranitidine, "Darnycya Ltd", Ukraine) at a dose of 100 mg/kg i.p., or over 2 and 3 days drug applying. The third group was similarly subdivided and A (Atropine, "Darnycya Ltd", Ukraine), at a dose of 3 mg/kg, i.p., the same time and doses. The fourth and fifth groups were administered R with A, and R with A and L-NAME (in dose 10 mg/kg, i.p.) In another series of experiments eCSE (Institute of Molecular Biology and Genetics of NASU) was introduced per os in 0.5 ml/200 g/day. IL-1beta, GRO/CINC-1 were detected by ELISA, NO serum content--by biochemical study. Rats with mESNR regulation by A blocking had an increase of IL-1beta by 32.8% over 2 days, 3 days a similar pretreatment level of GRO/CINC-1 increased by 13.9% vs control. Dual blocking of cholinergic and histaminergic mechanisms by combination of R with A--significant increase in the level of GRO/CINC-1 (by 137.1%). In the group with mESNR with combined blocking (R, A and L-NAME) accelerated production of IL-1beta (by 14.3%) and GRO/CINC-1 (by 191.4%) appeared after 3 days vs control. The NO serum content showed an increasing tendency with a maximum rise after 3 days of blocking of histaminergic and both cholinergic and histaminergic and a combination of triple blocking. The pre-treatment of eCMS showed an anti-inflammatory effect via a significantly decreased level of IL-1beta in rats with blocked cholinergic mechanism after one-day treatment. The results of the present study revealed that gastric acid suppression caused NEOL in rat OM, OEM. Plant-originated eCMS represented a mucosal protective effect on integrity of extragastral lesions manifestation, can be used as novel preventive therapeutic agent.