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Steroid hormones can modulate the endocannabinoid system (ECS). Within the female reproductive tract, estrogen increases the expression of the cannabinoid receptors CB1 and CB2, and modifies the levels of anandamide (AEA), the major endocannabinoid, by altering the expression of both AEA synthesis (NAPE-PLD) and catabolic enzymes (FAAH). Here, we addressed the mechanisms involved in ECS fluctuations within the central nervous system and evaluated the effects of tamoxifen (TAM), a selective estrogen receptor modulator, in central AEA regulation. The current results suggest that the hypothalamic and pituitary AEA levels change differently according to the brain area and phase of the estrous cycle. In TAM-treated rats, there is a disruption of the cyclic fluctuation and reduction of the AEA levels in all brain areas. In the pituitary gland, NAPE-PLD expression increases in the metestrus phase, whereas throughout the rat cycle their expression remained constant, even upon TAM treatment. The fluctuations of pituitary AEA levels result from altered FAAH and NAPE-LPD expression. In contrast, no differences in FAAH or NAPE-PLD hypothalamic expression were observed. Overall, this study presents a broad view of the distribution and expression of ECS elements in the central nervous system and a way to suggest possible brain areas involved in the interaction of the endocannabinoid and neuroendocrine systems to induce several behavioral responses.

Present study was undertaken to evaluate the analgesic activity of the ethanol extract of Chrysopogon aciculatus. In addition to bioassays in mice, chemical profiling was done by LC-MS and GC-MS to identify phytochemicals, which were further docked on the catalytic site of COX-2 enzymes with a view to suggest the possible role of such phytoconstituents in the observed analgesic activity. Analgesic activity of C. aciculatus was evaluated by acetic acid induced writhing reflex method and hot plate technique. Phytochemical profiling was conducted using liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS). In docking studies, homology model of human COX-2 enzyme was prepared using Easy Modeler 4.0 and the identified phytoconstituents were docked using Autodock Vina. Preliminary acute toxicity test of the ethanol extract of C. aciculatus showed no sign of mortality at the highest dose of 4,000 mg/kg. The whole plant extract significantly (p < 0.05) inhibited acetic acid induced writhing in mice at the doses of 500 and 750 mg/kg. The extract delayed the response time in hot plate test in a dose dependent manner. LC-MS analysis of the plant extract revealed the presence of aciculatin, nudaphantin and 5α,8α-epidioxyergosta-6,22-diene-3β-ol. Three compounds namely citronellylisobutyrate; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and nudaphantin were identified in the n-hexane fraction by GC-MS. Among these compounds, six were found to be interacting with the binding site for arachidonic acid in COX-2 enzyme. Present study strongly supports the traditional use of C. aciculatus in the management of pain. In conclusion, compounds (tricin, campesterol, gamma oryzanol, and citronellyl isobutyrate) showing promising binding affinity in docking studies, along with previously known anti-inflammatory compound aciculatin can be held responsible for the observed activity.