Neomenthol, a cyclic monoterpenoid, is a stereoisomer of menthol present in the essential oil of Mentha spp. It is used in food as a flavoring agent, in cosmetics and medicines because of its cooling effects. However, neomenthol has not been much explored for its anticancer potential. Additionally, targeting hyaluronidase, Cathepsin-D, and ODC by phytochemicals is amongst the efficient approach for cancer prevention and/or treatment.
To investigate the molecular and cell target-based antiproliferative potential of neomenthol on human cancer (A431, PC-3, K562, A549, FaDu, MDA-MB-231, COLO-205, MCF-7, and WRL-68) and normal (HEK-293) cell lines.
The potency of neomenthol was evaluated on human cancer and normal cell line using SRB, NRU and MTT assays. The molecular target based study of neomenthol was carried out in cell-free and cell-based test systems. Further, the potency of neomenthol was confirmed by quantitative real-time PCR analysis and molecular docking studies. The in vivo anticancer potential of neomenthol was performed on mice EAC model and the toxicity examination was accomplished through in silico, ex vivo and in vivo approaches.
Neomenthol exhibits a promising activity (IC50 17.3 ± 6.49 μM) against human epidermoid carcinoma (A431) cells by arresting the G2/M phase and increasing the number of sub-diploid cells. It significantly inhibits hyaluronidase activity (IC50 12.81 ± 0.01 μM) and affects the tubulin polymerization. The expression analysis and molecular docking studies support the in vitro molecular and cell target based results. Neomenthol prevents EAC tumor formation by 58.84% and inhibits hyaluronidase activity up to 10% at 75 mg/kg bw, i.p. dose. The oral dose of 1000 mg/kg bw was found safe in acute oral toxicity studies.
Neomenthol delayed the growth of skin carcinoma cells by inhibiting the tubulin polymerization and hyaluronidase activity, which are responsible for tumor growth, metastasis, and angiogenesis.

BACKGROUND: Unplanned postoperative reintubation (UPR) is a marker for severe adverse outcomes following general and vascular surgery.
METHODS: A retrospective analysis of 8809 adult patients, aged 18 years and older, who underwent major general and vascular surgery at a large single-center urban hospital was conducted from January 2013 to September 2016. Patients were grouped into those who experienced UPR and those who did not. Univariate and multivariate regression analyses were used to identify predictors of UPR, and association of UPR with adverse postoperative outcomes. All regression models had Hosmer-Lemeshow P > 0.05, and C-statistic >0.75, indicating excellent goodness-of-fit and discrimination.
RESULTS: Of the 8809 patients included, 138 (1.6%) experienced UPR. There was no statistical difference in incidence of UPR between general and vascular surgery patients (p = 0.53). Independent predictors of UPR advanced age (OR 5.1, 95%CI 3.5-7.5, p < 0.01), higher ASA status (OR 7.9, 95%CI 5.6-11.1, p < 0.01), CHF (OR 7.0, 95%CI 3.6-13.9, p = 0.02), acute renal failure or dialysis (OR 3.1, 95%CI 1.8-5.7, p = 0.01), weight loss (OR 5.2, 95%CI 2.8-9.6, p = 0.01), systemic sepsis (OR 4.8, 95%CI 3.4-6.9, p < 0.01), elevated preoperative creatinine (OR 4.2, 95%CI 3.0-5.9, p = 0.01), hypoalbuminemia (OR 5.3, 95% CI 3.8-7.5, p = 0.01), and anemia (OR 4.0, 95%CI 2.8-5.9, p < 0.01). Following surgery, UPR was associated with increased mortality (OR 3.8, 95%CI 2.7-5.2, p < 0.01), pulmonary complications (OR 1.8, 95%CI 1.7-2.0, p < 0.01), renal complications (OR 2.6, 95%CI 1.7-3.5, p < 0.01), cardiac complications (OR 4.6, 95%CI 2.0-6.7, p < 0.01), postoperative RBC transfusion (OR 5.7, 95%CI 3.8-8.6,p < 0.01), and prolonged hospitalization (OR 1.8, 95%CI 1.5-2.4, p < 0.01).
CONCLUSIONS: UPR is significantly associated with postoperative morbidity and mortality. Perioperative management aimed at decreasing incidences of UPR after noncardiac surgery should target preoperative anemia in addition to previously identified predictors.