(Rac)-Anemonin

(Rac)-Anemonin ((Rac)-Pulsatilla camphor; (Rac)-Anemonine) is an isomer of Anemonin. Anemonin is a naturally occurring bislactone small molecule derived from Ranunculaceae with blood-brain barrier permeability, possessing a variety of activities including anti-inflammatory, antioxidant, neuroprotective, melanogenesis-inhibiting, and antiparasitic effects. Anemonin inhibits iNOS to reduce NO release; it inhibits PKC-θ protein expression and downregulates the pro-inflammatory factors TNF-α, IL-1β, and IL-6; it enhances the activities of the antioxidant enzymes SOD, CAT, and GSH-Px, and reduces MDA and ROS levels. Anemonin modulates the Bcl-2 / Bax / caspase-3 pathway to inhibit apoptosis; it downregulates melanogenesis-related molecules including MITF, TYR, TRP1, and TRP2, thereby inhibiting melanin synthesis in human melanocytes. Anemonin inhibits Leishmania and Schistosoma mansoni. Anemonin is used in research related to diseases such as hyperpigmentation, cerebral ischemia/reperfusion injury, inflammation, sepsis-induced acute lung injury, acute ulcerative colitis, leishmaniasis, and schistosomiasis^{[1][2][3][4][5][6]}. In Vitro:Anemonin exhibits low cytotoxicity in human melanocytes, with cell viability remaining above 96% at 50 μM^[1].
Anemonin (10-50 μM; 8-48 h) inhibits cellular tyrosinase activity in human melanocytes in a concentration- and time-dependent manner, with an IC₅₀ of 43.4 μM^[1].
Anemonin (20-50 μM; 8-48 h) reduces melanin content in human melanocytes; it decreases TYR, TRP1, and TRP2/DCT protein expression in human melanocytes in a dose- and time-dependent manner, particularly affecting TYR and TRP2^[1].
Anemonin (20-50 μM; 24 h) downregulates the mRNA expression of TYR, TYRP1, and TYRP2 in human melanocytes in a dose-dependent manner^[1].
Anemonin (20-40 μM; 24 h) downregulates MITF mRNA expression in human melanocytes in a dose-dependent manner^[1].
Anemonin does not affect the viability of LPS-treated RAW 264.7 macrophages even at 100 μM^[3].
Anemonin (2.5-30 μM; 24 h) inhibits LPS-induced NO production in RAW 264.7 macrophages with an IC₅₀ of 5.37 μM^[3].
Anemonin (2.5-30 μM; 24 h) inhibits iNOS protein expression in LPS-induced RAW 264.7 macrophages in a concentration-dependent manner^[3].
Anemonin (2.5-30 μM; 6 h) inhibits LPS-induced iNOS mRNA expression in RAW 264.7 macrophages in a concentration-dependent manner, without affecting GAPDH mRNA expression^[3].
Anemonin (2.5-10 μM; 48 h) shows no cytotoxicity in HT-29 cells and attenuates LPS-induced inflammation in HT-29 cells by downregulating the expression of IL-1β, TNF-α, and IL-6 in a dose-dependent manner^[5].
Anemonin (2.5-10 μM; 24 h) is not cytotoxic to LPS-stimulated MH-S and MLE-12 cells^[4].
Anemonin (2.5-10 μM; 24 h) dose-dependently inhibits LPS-induced TNF-α, IL-1β, and IL-6 mRNA expression and secretion in MH-S and MLE-12 cells; combination with the NF-κB inhibitor PDTC enhances the inhibition of inflammatory responses; the anti-inflammatory effect is suppressed under Nrf2 knockdown^[4].
Anemonin (2.5-10 μM; 24 h) inhibits LPS-induced activation of the NF-κB pathway and enhances activation of the Nrf2/HO-1 pathway in MH-S and MLE-12 cells^[4].
Anemonin (2.5-10 μM; 24 h) reverses LPS-induced oxidative stress in MH-S and MLE-12 cells by decreasing MDA content and increasing SOD and CAT activities^[4].
Anemonin (2.5-10 μM) inhibits PKC-θ protein expression in a dose-dependent manner in HT-29 cells without affecting PRKCQ gene transcription, significantly reduces TNF-α mRNA levels, and exerts no significant effect on PRKCQ and PTPN2 gene transcription; PRKCQ overexpression reverses the inhibitory effects of Anemonin on cytokine mRNA production and cytokine protein production in HT-29 cells^[5].

Anemonin (0.00565-1000 µg/mL; 48 h) exhibits a CC₅₀ of 5.39 µg/mL (28.00 nM) against mouse peritoneal macrophages and shows hemolytic activity against human erythrocytes with an LC₅₀ of 91.00 µg/mL (473.95 nM)^[6].
Anemonin (0.000565-100 µg/mL; 72 h) exhibits potent anti-promastigote activity against L. aethiopica and L. donovani with IC₅₀ values of 0.257 µg/mL (1.33 nM) and 0.303 µg/mL (1.58 nM), respectively; and exhibits potent anti-amastigote activity against L. aethiopica and L. donovani with IC₅₀ values of 0.239 µg/mL (1.24 nM) and 0.368 µg/mL (1.91 nM), respectively^[6].
Anemonin (1-10 µM; 72 h) exhibits high antischistosomal activity against S. mansoni NTS, with activity of 93.75% at 10 µM and 41.38% at 1 µM; it exhibits moderate antischistosomal activity against adult S. mansoni, with activity of 48.95% at 10 µM^[6]. In Vivo:Anemonin (150 mg/kg; i.p.; once daily; 7 days) provides significant neuroprotective effects against cerebral I/R injury in rats by enhancing antioxidant activity and inhibiting apoptotic pathways^[2].
Anemonin (150 mg/kg; i.p.; single administration) penetrates the blood-brain barrier in rats and reaches a maximum brain-to-plasma partition coefficient (R_i) of 0.7 at 90 min after administration^[2].
Anemonin (5-100 μM; incubation; 6 h for endothelium-denuded rings, 20 min for endothelium-intact rings) reverses LPS-induced hyporeactivity of blood vessels to phenylephrine without affecting eNOS-mediated endothelium-dependent relaxation, which is consistent with selective inhibition of iNOS^[3].
Anemonin (10 mg/kg; i.p.; single injection simultaneously with LPS) attenuates sepsis-induced acute lung injury in mice by inhibiting inflammatory responses and oxidative stress^[4].
Anemonin (10 mg/kg; i.p.) reduces LPS-induced mortality in a mouse model of sepsis-induced ALI^[4].
Anemonin (2-10 mg/kg; i.p.; daily; 7 days) alleviates DSS-induced acute ulcerative colitis in mice by inhibiting colonic tissue inflammation and suppressing PKC-θ protein expression^[5].