Achyranthes aspera ameliorates stress induced depression in mice by regulating neuroinflammatory cytokines.

Background and aim: Achyranthes aspera Linn. (A. aspera) (family: Amaranthaceae) is highly recognized in ethnomedicine and traditional systems of Indian medicine as a nervine restorative for several psychiatric disorders. Study presented here was designed to appraise the antidepressant-like effects of A. aspera in murine model of chronic unpredictable mild stress (CUMS) induced depression. Experimental procedures-: Rodents were exposed to different stressor in unpredictive manner during CUMS protocol once a day for 4 weeks. Mice were intraperitoneally injected with A. aspera extract (2.5, 5 and 10 mg/kg) or fluoxetine (10 mg/kg) or betaine (20 mg/kg) once daily during day 15-28 of the CUMS protocol. Sucrose preference, motivation and self-care, immobility latency and plasma corticosterone were evaluated after 24 h of last stressor. After behavioral assessments TNF-α, Il-6 and BDNF immunocontent was determined in hippocampus and prefrontal cortex. Results and conclusion: A. aspera extract as well as betaine improved sucrose preference, increased grooming frequency and latency in splash test and ameliorated depression-like condition in CUMS mice in Porsolt test. A. aspera treatment decreased the elevated plasma corticosterone and reversed the effect of CUMS on TNF-α, Il-6 and BDNF immunocontent in mice. The results of the present study suggest A. aspera as a promising indigenous medicine for stress associated neurobehavioral and comorbid complications.

Lumefantrine solid dispersions with piperine for the enhancement of solubility, bioavailability and anti-parasite activity.

Crystallinity and P-glycoprotein (P-gp) mediated efflux of drugs with low aqueous solubility collaboratively contributes to erratic absorption resulting in low/variable bioavailability. Herein, the amorphous solid dispersions (SD) of lumefantrine (LUMF) containing piperine (PIP), a P-gp and CYP3A4 inhibitor, were formulated with Soluplus (Sol), Klucel (Klu) and Lutrol F68 (Lut), polymeric carriers, to improve solubility and bioavailability of LUMF following oral administration. The LUMF-PIP-SD prepared with Sol exhibited higher aqueous solubility of LUMF in concentration dependent manner and LUMF-PIP-Sol demonstrating maximum aqueous LUMF solubility were characterized by DSC, FTIR and XRD. The DSC thermogram and XRD diffractogram of LUMF-PIP-SD confirmed the loss of crystallinity of LUMF ensuing improved dissolution while possible interaction of LUMF with PIP and /or Sol was evident in FTIR spectrum. DSC and dissolution studies confirmed the stability for LUMF-PIP-Sol SD stored for 90 days under stressed conditions of humidity and temperature. An in situ single-pass intestinal perfusion study in rats indicated 2.2-fold increase in intestinal permeation of LUMF co-administered with PIP. Improved bioavailability of LUMF was evidenced by increased AUC0-∞ and Cmax for LUMF in SD compared to alone LUMF or LUMF with PIP. Peter's four-day suppressive test indicated improved antimalarial activity for LUMF-PIP-Sol SD. Overall, the data suggest that the SD of LUMF incorporated with P-gp inhibitor PIP, improves the bioavailability as well as antimalarial efficacy of LUMF.

Allicin, a SUR2 opener: possible mechanism for the treatment of diabetic hypertension in rats

The garlic (Allium sativum L., Amaryllidaceae) has been popularly used in the treatment of diabetes and cardiac complications. In the present work, we have studied the possible mechanisms, sulfonylurea receptor (SUR) selectivity of allicin in diabetic hypertensive rats. Diabetic hypertension was induced by intraperitoneal injection of streptozotocin (50 mg/kg) followed by daily administration of dexamethasone (10 µg/kg, s.c.). Different parameters, blood pressure and blood glucose levels were studied in the rats weekly up to eight weeks. Allicin (8 mg/kg, p.o.) shows potent antidiabetic (*p<0.001) as well as antihypertensive effect (**p<0.001, *p<0.01). It may act as a vasodilator by hyperpolarizing the membrane of normal vascular smooth muscle cells. The hyperpolarization in vascular smooth muscle occurs due to K+ channel opener activity. Antihypertensive effect of allicin is inhibited by glibenclamide, nonselective SUR blocker while combination of allicin with nateglinide, selective SUR1 blocker exerted synergistic antihypertensive effect. The results indicates that allicin is effective in the treatment of diabetic hypertension; through a mechanism that might involve selective opening of SUR2.