piperine and Colitis--Ulcerative

Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medicinal use. Piperine exhibits antidepressant, hepatoprotective, anti-metastatic, anti-thyroid, immunomodulatory, antitumor and anti-inflammatory activities, However its therapeutic potential in amelioration of ulcerative colitis and the underlying mechanism for anti-inflammatory activity remains unknown.The objective of the present investigation was to unravel the therapeutic potential of piperine on amelioration of IBD using acetic acid induced experimental animal model for ulcerative colitis and to determine the role of TLR4 receptor in signalling pathway of inflammatory gene expression in ulcerative colitis.. We induced colitis using acetic acid (150µl of 5% once, intrarectally) in mice and estimated disease activity index (DAI), which took into account weight loss, stool consistency, and occult/gross bleeding. Colon length, spleen weights, ulcer area and ulcer index were measured; histological changes were observed by H&E staining. Effect of piperine on various antioxidant parameter of mice colon such as tissue myeloperoxidase (MPO) accumulation, SOD concentrations, reduced GSH and lipid peroxidation were determined. Pro-inflammatory mediators, namely, nitric oxide (NO), tumour necrosis factor-α (TNF-α) were determined by a TNF-α ELISA kit obtained from Thermo fisher scientific India Pvt. Ltd. Effect of piperine on haematological parameters of mice in acetic acid induced IBD was also determined which involves the estimation of FFA using a commercial free fatty acid fluorometric assay kit.. Piperine significantly attenuated acetic acid induced DAI score which implies that it suppresses weight loss, diarrhoea, gross bleeding and infiltration of immune cells. Piperine administration also effectively and dose dependently prevented shortening of colon length and enlargement of spleen size. Histological examination indicated that piperine reduces oedema in sub-mucosa, cellular infiltration, reduced haemorrhages and ulceration as compare to acetic acid induced colitis in mice. Furthermore piperine inhibited abnormal secretion of pro-inflammatory mediators namely NO, cytokines TNF-α and reduces FFA induced TLR4 mediated inflammation.. These results suggest that piperine has an anti-inflammatory effect at colorectal sites that is due to down- regulations of the productions and expression of inflammatory mediators and it also reduces FFA induced TLR4 mediated inflammation. Thus it may have therapeutic potential on amelioration of IBD.

Topics: Acetic Acid; Alkaloids; Animals; Anti-Inflammatory Agents; Benzodioxoles; Colitis, Ulcerative; Colon; Fatty Acids, Nonesterified; Glutathione; Lipid Peroxidation; Male; Malondialdehyde; Mice; Nitric Oxide; Piperidines; Polyunsaturated Alkamides; Superoxide Dismutase; Toll-Like Receptor 4; Toxicity Tests, Acute; Tumor Necrosis Factor-alpha

Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system (SMEDDS) to improve the stability and water-solubility of CUR and enhance its anti-colitis activity. The formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic components CUR and PIP, and then was characterized by assessing appearance, morphology, particle size, zeta potential and drug encapsulation efficiency. The appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation. The mean size of microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 ± 0.76 nm, and the drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 ± 2.18)% and (90.78 ± 2.56)%, respectively. The vitro stability investigation of CUR-PIP-SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co-encapsulated with PIP, CUR was more stable than drug solution in colons site. Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS-induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue through retention enema administration. Our study illustrated that the developed CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific drug delivery system of CUR for ulcerative colitis treatment.

Topics: Alkaloids; Animals; Benzodioxoles; Chemistry, Pharmaceutical; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Drug Stability; Emulsions; Male; Mice; Mice, Inbred BALB C; Particle Size; Piperidines; Polyunsaturated Alkamides; Solubility

The present work was undertaken to determine the effects of Amaranthus roxburghianus Nevski. (Amaranthaceae) root alone and in combination with piperine in treating ulcerative colitis (UC) in mice.. Swiss albino mice were divided into seven groups (n = 6). Standard group received prednisolone (5 mg/kg, intraperitoneally). Treatment groups received hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, per oral) and a combination of hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, per oral) and piperine (5 mg/kg, per oral). Ulcer index, colitis severity, myeloperoxidase (MPO), malondialdehyde and glutathione were estimated from blood and tissue. Column chromatography of the extract was done and purified fractions were analyzed by gas chromatography-mass spectroscopy (GC-MS).. Treatment with the combination of hydroalcoholic extract of A. roxburghianus and piperine showed minimal ulceration, hemorrhage, necrosis and leucocyte infiltration by histopathological observation. Acetic acid increased MPO levels in blood and colon tissue to 355 U/mL and 385 U/mg, respectively. The combination of hydroalcoholic extract of A. roxburghianus (100 mg/kg) and piperine (5 mg/kg) significantly decreased MPO in blood and tissue to 182 U/mL and 193 U/mg, respectively (P < 0.05). Similarly, this combination significantly reduced malondialdehyde levels and increased glutathione levels in blood and tissue. Various phytoconstituents were detected by GC-MS.. The combination of hydroalcoholic extract of A. roxburghianus and piperine is effective in the treatment of UC and the effects are comparable with the standard drug prednisolone. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, eugenol and benzene, and 1-(1,5-dimethyl-4-hexenyl)-4-methyl are reported having analgesic, anti-inflammatory, and antioxidant properties; they may play a role in the biological activity of A. roxburghianus root.

Topics: Alkaloids; Amaranthus; Animals; Benzodioxoles; Colitis, Ulcerative; Colon; Drug Therapy, Combination; Glutathione; Humans; Male; Malondialdehyde; Mice; Peroxidase; Piperidines; Plant Extracts; Plant Roots; Polyunsaturated Alkamides