Plausible role of carveol in gastrointestinal disorders: Mechanistic insights via H+/K+-ATPase and voltage-gated calcium channel inhibition.

This research sought to develop a pharmacological foundation for assessing the impact of the monoterpenoid carveol on multiple gastrointestinal diseases. The in-silico studies were done using SwissADME, AUTODOCK, PyRx and Desmond software package. Further research on the antidiarrheal, antisecretory, charcoal meal transit time, anti-spasmodic, anti-ulcer, and anti-H. pylori properties of carveol was conducted using several models. The research was conducted after approval from the Riphah Institute of Pharmaceutical Sciences Research and Ethics Committee (Ref. no. REC/RIPS/2019/021). Carveol at doses of 10, 30 and 50 μg/kg has successfully minimized intestinal and diarrheal secretions as well as the charcoal meal transit time. Carveol inhibited H.pylori, act as a gastroprotectant in ethanol-induced gastric ulcer model. Furthermore, the related oxidative stress and inflammation associated with ulcers were mitigated by carveol treatment, which was evident by restoration of GST (Glutathione), GSH (Glutathione-S-transferase), CAT (catalase) and simultaneous inhibition of LPO (lipid peroxidation) alongside TNF-α and IL-8 through ELISA. The results were further confirmed by improvement in the gross appearance of the gastric tissues and its histopathology. Moreover, the ability of carveol to inhibit H+/K+-ATPase was confirmed by RT-PCR. In rabbit jejunum preparations it depicted a concentration-dependent response thereby reducing the spontaneous and high K+-generated contractions and calcium channels as depicted by a shift towards right in Ca2+-concentration curve, comparable to that of papaverine. Carveol was found to be an anti-oxidant, anti-inflammatory, anti-ulcer, antidiarrheal and antispasmodic agent at tested doses.