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Objective: To evaluate the effect of p-coumaric acid (p-CA) on haloperidol-induced catalepsy in Swiss albino male mice. Methods: To induce catalepsy, haloperidol (1 mg/kg i.p.) was administered for 21 consecutive days. p-CA (50, 75, and 100 mg/kg, PO) was administered 30 min before haloperidol injection for 21 consecutive days. For catalepsy, locomotor activity and motor coordination scores were recorded on the 17, 14, and 21 days of drug treatment, while the gait analysis score was recorded on day 21. After behavioral testing, animals were sacrificed, and various biochemical and histopathology tests of the brain were conducted. Dopamine, malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activity were examined in the brain. Results: Chronic administration of haloperidol significantly increased catalepsy in mice. It also produced hypolocomotion, motor coordination, and gait disturbance in mice. p-CA significantly inhibited haloperidol-induced catalepsy. Haloperidol significantly increased malondialdehyde levels in the brain. While dopamine levels in the brain dropped along with GSH, SOD, and catalase activity levels, which also had an impact on the histology of the brain. p-CA significantly reduced haloperidol-induced increases in brain oxidative stress, dopamine levels in the brain, and brain histology in mice. Discussion: p-CA significantly reduced haloperidol-induced catalepsy, possibly through reducing oxidative stress and increasing brain dopamine levels. It can be a good candidate drug for extrapyramidal symptoms in Parkinson's disease and adjuvant therapy with antipsychotic drugs. [ABSTRACT FROM AUTHOR]

The present study was performed to investigate the underlying defensive mechanisms of formononetin in nephrotoxicity by using in vivo and in vitro models. MTT assay was carried out to test the toxic effect of formononetin in HEK-293 cells which were treated with formononetin (5, 10, 20 µM) and cisplatin (20 µM). The concentrations of TNF-α and nitric oxide (NO) were determined in the cell supernatant. Nephrotoxicity in rats was induced by a single intraperitoneal injection of cisplatin at a dose of 5 mg/kg, and formononetin at doses of 10 and 30 mg/kg was used to study protective activity. Blood urea nitrogen (BUN), serum creatinine, oxidative strain, a proinflammatory cytokine, NO, and histological alteration were measured to find the therapeutic activity of formononetin. Cells treated with cisplatin showed increased levels of TNF-α and NO. Formononetin-treated cell lines showed a decreased level of TNF-α and NO production. In vivo studies determine that in the disease control group, the levels of proinflammatory cytokines, oxidative stress, BUN, and creatinine were increased because of cisplatin-induced nephrotoxicity. After the treatment of formononetin for 14 days, the levels of cytokines and oxidative stress were reduced in the test control group as compared to the disease control group. The inhibitory action of formononetin on inflammatory responses was achieved by reducing the expressions of cytokines. Cisplatin-treated rats showed the altered structure of kidney tissue; meanwhile, formononetin normalizes the structure of kidney tissue. From our findings, we conclude that formononetin has therapeutic potential in renal complications like nephrotoxicity, by inhibiting the production of proinflammatory cytokines (i.e., TNF-α) and oxidative stress (i.e., NO) in HEK-293 cell lines as well as protecting the rats from nephrotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the hypolipidemic potential of the 70 % ethanol fruit extract of Prosopis cineraria (Fabaceae) (Et. PCF) in triton-induced hyperlipidemia in rats. Methods: Et-PCF was obtained by pulverizing whole dried fruits and extracting with 70 % ethanol. Adult Sprague Dawley rats were divided into six groups of six rats each. The groups were namely normal control, hyperlipidaemic control, standard drug-treated (simvastatin 4 mg/kg), and three Et-PCF (200, 400 and 600 mg/kg, respectively)-treated groups. Apart from normal control, all other groups received a single dose of triton (200 mg/kg, i.p.) exactly 30 min after a dose of the standard drug and Et-PCF for the induction of hyperlipidemia. Twenty four hours after triton injection, hyperlipidemia was confirmed by collecting blood samples from all the rats and testing for serum lipid profile. Antioxidant activity, in the form of inhibition of lipid peroxidation, was determined along with chromatographic analysis. Moreover, molecular docking study of β-sitosterol (active constitute of PCF) was performed with Farnesoid X receptor. Results: Triton-induced hyperlipidemia group showed significant increase in total cholesterol, low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL) , triglyceride, atherogenic index and decreased high density lipoprotein cholesterol (HDL), compared to normal control group. Et-PCF treated groups showed reduction in serum cholesterol, triglyceride, VLDL and LDL levels compared to triton treated control group. Extract at the dose of 200 mg/kg significantly reduce serum cholesterol (p < 0.01) and serum LDL (p < 0.01). At the dose level of 400 mg/kg and 600 mg/kg extract is effective to significantly reduce serum cholesterol (p < 0.05), triglyceride (p < 0.05), VLDL (p < 0.05), LDL (p < 0.05) and atherogenic index (p < 0.05) and these results are almost equivalent to those of standard drug simvastatin. Furthermore, antioxidant activity, i.e., IC50 of Et-PCF was 58.33 μg/ml. Molecular docking score of β-sitosterol for Farnesoid X receptor was -8.32 kcal/mol, suggesting excellent binding conformation of Et-PCF to receptor molecules. Conclusion: The findings suggest that Prosopis cineraria may be beneficial for preventing hyperlipidaemic complications by its anti-hyperlipidemic and antioxidant activities. [ABSTRACT FROM AUTHOR]

[Display omitted] • Solid SNEDDS of MH was prepared by physical adsorption method. • Flowability of solid SNEDDS was investigated by powder flow tester. • Solid state characterization confers transformation of crystalline to amorphous. • In vitro- In vivo studies revealed an improvement of dissolution & bioavailability. • The estimated shelf life of solid SNEDDS of MH was found to be 27.57 months. Morin hydrate (MH) is a promising flavonoid with diverse biological activities; unfortunately, it finds limited clinical application due to its low water solubility. Herein, we developed a liquid self nano-emulsifying drug delivery system (l -SNEDDS) employing Labrafil M 1994 CS, Cremophor RH 40, and Transcutol HP. The l -SNEDDS has been solidified by physical adsorption using inert carriers, i.e., Neusilin US2 and Aerosil 200. The S-SNEDDS was thoroughly investigated for flow function (FF), effective angle of wall friction (EAWF), and effective angle of internal friction (EAIF) employing a powder flow tester (PFT). The solid-state characterizations of S-SNEDDS were performed using FTIR, DSC, PXRD, and SEM. Further, in vitro dissolution, in vivo pharmacokinetic, and shelf life estimation were performed on selected SOF-2 formulation. The SOF-2 reveals good emulsifying ability, particle size (52 ± 4.25 nm), and PDI (0.133 ± 0.06). The FF and Jenike's classification suggests the "free-flowing" nature of S-SNEDDS prepared using Neusilin US2. Further, S-SNEDDS prepared using Neusilin US2 showed a low friction angle, i.e., EAWF and EAIF, than Aerosil 200, therefore, a better flowability. The solid-state characterization of SOF-2 demonstrated the transition of MH from crystalline to amorphous state and good compatibility between MH and Neusilin US2. Further, SOF-2 showed more dissolution than pure MH and subsequently 2.97-fold increments in its oral bioavailability. Moreover, the shelf life of SOF-2 was reported to be 27.57 months, suggesting its excellent physical and chemical stability. In brief, solidifying l -SNEDDS and investigating flow behaviors by PFT could find attention in the pharmaceutical and food industry for commercial purposes. [ABSTRACT FROM AUTHOR]