Administration Of Piperine Research Articles

Systemic administration of curcumin or piperine enhances the periodontal repair: a preliminary study in rats.

Studies have documented the anti-inflammatory effects of spices, which may be related to treatment of chronic diseases. The purpose of this study was to evaluate the influence of curcumin and piperine and their association on experimental periodontal repair in rats. Periodontitis was induced via the installation of a ligature around the first molar. After 15days, the ligatures were removed, and the rats were separated into groups (12 animals per group): (i) curcumin, (ii) piperine, (iii) curcumin+piperine, (iv) corn oil vehicle, and (v) control group (animals had ligature-induced periodontitis but were not treated). The compounds were administered daily, for 15days by oral gavage. Animals were euthanized at 5 and 15days, and hemimaxillae and gingival tissues were harvested. Bone repair was assessed by μCT (microcomputer tomography). Histological sections were stained with hematoxylin/eosin (H/E) for the assessment of cellular infiltrate or picrosirius red for quantification of collagen content, and subjected to immunohistochemistry for detecting NF-ĸB. Gingival tissues were used to evaluate levels of TGF-β and IL-10 (ELISA). Curcumin and piperine increased the TGF-β level, significantly improved the collagen repair, and decreased the cellularity and activation of NF-ĸB in the periodontal tissues, but only curcumin caused a significant increase in early bone repair. Curcumin and piperine promoted a substantive effect on tissue repair; however, there was not synergistic effect of compounds administered in combination. Curcumin and piperine stimulates the tissue repair and may be potential candidates for the treatment of periodontal disease.

Chronic administration of piperine attenuates behavioural, biochemical and histological alterations induced by intracerebroventricular streptozotocin in rats

The above article, published online on 11 June 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13052), has been withdrawn by agreement between the journal Editor in Chief, Prof. Kim Brøsen, the corresponding author and Wiley Publishing. The withdrawal has been agreed due to the article having been submitted to multiple journals at the same time.

Absence of adverse effects following administration of piperine in the diet of Sprague-Dawley rats for 90 days

Piperine (E,E-) is a naturally occurring pungent and spicy constituent of black pepperand is also used as an added flavoring ingredient to foods and beverages. Piperine has been determined safe under conditions of intended use as a flavoring substance by regulatory and scientific expert bodies. While concurring with the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and Flavor and Extract Manufacturers Association (FEMA) Expert Panel on the safety of piperine, the European Food Safety Authority (EFSA) requested additional toxicological data. The results of a 90-day GLPcompliant dietary study, conducted in Sprague-Dawley rats at target doses of 0, 5, 15, or 50 mg/kg bw/day, to respond to this request are presented herein. No adverse effects were found attributable to ingestion of piperine. Statistically significant changes in food consumption, body weight gain, and plasma cholesterol levels were not considered adverse as discussed in this paper. Therefore, the oral no-observed-adverse-effect level (NOAEL) was determined to be the highest dose tested of 50 mg/kg bw/day. EFSA derived a lower NOAEL of 5 mg/kg bw/day based on increased plasma cholesterol levels which still affords an adequate margin of safety of over 48,000 and concluded that piperine is not of safety concern.

Piperine Promotes Glucose Uptake through ROS-Dependent Activation of the CAMKK/AMPK Signaling Pathway in Skeletal Muscle.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing yearly worldwide. Glycemic control is the basis for the treatment of T2DM, as it can prevent the progress of associated complications. Spices possess various health beneficial effects on humans. The aim of this study is to search for spices that can promote glucose uptake and to elucidate the underlying molecular mechanism(s). Among 24 spice extracts, the extracts from black pepper and white pepper significantly increase glucose uptake in L6 myotubes. Piperine is found to be the active compound in these extracts. Treatment of myotubes with piperine induces the translocation of glucose transporter 4 (GLUT4) to the plasma membrane by phosphorylation of AMP-activated protein kinase (AMPK). Piperine increases the intracellular Ca2+ level and reactive oxygen species (ROS) generation through transient receptor potential vanilloid channel 1 (TRPV1), followed by activation of Ca2+ /calmodulin-dependent protein kinase kinase-beta (CaMKKβ) as the upstream events for AMPK phosphorylation. Furthermore, oral administration of piperine to Wistar rats at 0.01 and 0.1mg kg-1 body weight decreases postprandial hyperglycemia accompanied by GLUT4 translocation and AMPK phosphorylation. Piperine in pepper prevents hyperglycemia by GLUT4 translocation through CaMKKβ/AMPK signaling via TRPV1-dependent increase in the intracellular Ca2+ level and ROS generation.

Beneficial Effects of Piperine in global cerebral ischemia/reperfusion model in irradiated rats

Stroke is the third cause of death and a leading cause of chronic disability all around the world. Inflammation and oxidative stress are common pathogenic pathways of brain injury induced by ischemia/reperfusion (I/R). This work aims to investigate the possible role of Piperine as antioxidant and anti-inflammatory in attenuating the cerebral ischemia/reperfusion (I/R)-induced brain injury in whole body γ-irradiated rats. Global cerebral ischemia was induced in both irradiated and non-irradiated male Wistar rats, and was followed by reperfusion. The beneficial effect of pretreatment with piperine (10 mg/kg, once daily p.o. for 15 days) was examined on cerebral ischemia-induced brain injury in 24 h pre-irradiated (6 Gy) male Wistar rats. I/R increased brain content of malondialdehyde (MDA) and decreased its glutathione (GSH) content and total antioxidant capacity (TAC). It also raised serum lactate dehydrogenase (LDH) activity and brain cytosolic calcium (Ca2+) level. Pre-treatment with piperine significantly attenuated brain injury in I/R irradiated rats by decreasing cytosolic brain calcium level and serum lactate dehydrogenase (LDH) activity. In addition, a significant decrease in nuclear factor kappa-B (NF-kB) was recorded in piperine treated group. These findings indicate that administration of piperine ameliorated most of the tested biochemical changes induced by I/R in irradiated rat brain and serum.

Enhanced anti-tumor efficacy and mechanisms associated with docetaxel-piperine combination-in vitroandin vivoinvestigation using a taxane-resistant prostate cancer model

Docetaxel (DTX) is widely used for metastatic castrated resistant prostate cancer, but its efficacy is often compromised by drug resistance associated with low intracellular concentrations. Piperine (PIP) could enhance the bioavailability of other drugs via the inhibition of CYPs and P-gp activities. Thus, we hypothesize a positive effect with the DTX-PIP combination on the anti-tumor efficacy and intra-tumor DTX concentrations in taxane-resistant prostate cancer. ICR-NOD/SCID mice implanted with taxane-resistant human prostate cancer cells were administrated with saline as well as PIP and DTX separately or in combination. The tumor growth was monitored together with intra-tumor concentrations of DTX. The inhibitory effects on CYPs and P-gp were further assessed in mouse liver microsome and MDCK-MDR1 cells. Compared with DTX alone, DTX-PIP combination significantly inhibited the tumor growth (114% vs. 217%, p = 0.002) with corresponding significantly higher intra-tumor DTX concentrations (5.854 ± 5.510 ng/ml vs. 1.312 ± 0.754 ng/mg, p = 0.037). The percentage of DTX metabolism was significantly decreased from 28.94 ± 1.06% to 18.14 ± 2.22% in mouse liver microsome after administration of PIP for two weeks. DTX accumulation in MDCK-MDR1 cell was significantly enhanced in the presence of PIP. Further microarray analysis revealed that PIP inhibited P-gp as well as CYP1B1 gene expression and induced a significant gene expression change relating to inflammatory response, angiogenesis, cell proliferation, or cell migration. In conclusion, DTX-PIP combination significantly induces activity against taxane-resistant prostate tumor. Such effect appeared to be attributed to the inhibitory effect of PIP on CYPs and P-gp activity as well as gene expression changes relating to tumorigenesis and cellular responses.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.

Objective(s):In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue.Materials and Methods:Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies.Results:The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats.Conclusion:From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

Effect of Co-administration of Single and Multiple Doses of Piperine on the Pharmacokinetics of Tamoxifen in Rats

The aim of this study was to investigate the effect of single and multiple oral administration of piperine on the pharmacokinetics of tamoxifen in rats. Tamoxifen was administered orally alone at 10 mg/kg or with singles (10, 25 and 50 mg/kg) or multiple (10 mg/kg) oral doses of piperine. In the present study, compared with the control group (tamoxifen alone) and piperine single and multiple dose administration showed significant increase in AUC 0-∞ and t 1/2 . The relative bioavailability of tamoxifen in the piperine treated groups was 2.15-2.39 times higher compared to control group. The present study revealed that piperine significantly improved bioavailability of tamoxifen and the influence of piperine on the pharmacokinetics of tamoxifen may be attributed to the inhibition of metabolism of tamoxifen.

Piperine ameliorates collagenase-induced Achilles tendon injury in the rat

ABSTRACTTendinopathy is a common clinical pathology found in athletes and workers with mixed treatment results. Piperine, a major alkaloid found in the black and long pepper, has been demonstrated to have variety of pharmacological properties such as analgesic and anti-inflammatory effects. The present study was designed to investigate the effects of piperine on collagenase-induced Achilles tendon injury. Rats were intratendineously injected with collagenase in the right Achilles tendon, followed by intragastrical administration of piperine (100 mg/kg). Morphological structure and biochemical analysis of glycosaminoglycans, hydroxyproline, collagen III, and the activity of matrix metallopeptidases in the tendon tissues were performed. Our results showed that collagenase injection resulted in clear degenerative changes in the tendon. Administration of piperine improved the morphological structure of tendon, increased glycosaminoglycans and hydroxyproline levels, and inhibited the expression and activities of MMP-2 and MMP-9. Furthermore, piperine inhibited the activation of ERK and p38 signaling pathways in injured tendon. These results indicate a beneficial role of piperine against collagenase-induced tendon injury.

Vasculoprotective and vasodilatation effects of herbal formula (Sahatsatara) and piperine in spontaneously hypertensive rats

BackgroundThe herbal formula (Sahatsatara, STF), the Thai traditional poly-herbal recipe, has been used for treatment of muscle pain, anti-flatulence and numbness on hands and feet, with the caution when used in hypertensive patients. However, there is no scientific evidence to prove its effects on cardiovascular system. Piperine is the proposed major active compound in STF. It is shown to have antihypertensive effect in the L-NAME-induced endothelial dysfunction rats. PurposeThis study investigated the pharmacokinetics, mechanism of action, as well as the hemodynamic and vasoactive effect and toxicity of STF and piperine using spontaneously hypertensive rats (SHR) and normal Wistar rats (NWR). MethodsThe amount of piperine in STF was measured by ultra performance liquid chromatography (UPLC). SHR and NWR were gavaged with piperine (50mg/kg/day) or STF (100, 300, or 1000mg/kg/day) alone or together with L-NAME (in drinking water) for 28 days. Hemodynamic effects were monitored by noninvasive tail cuff every 7 days. Vasorelaxation effect on the thoracic aorta in organ chamber was observed through force transducer at the end of the experiment. Biochemical parameters for kidney and liver toxicity were measured. In addition, pharmacokinetic study was performed using non-compartment analysis. ResultsThe amount of piperine in STF was 1.29%w/w. Both STF and piperine did not affect blood pressure and heart rate in both SHR and NWR. Interestingly, STF and piperine increased acetylcholine-induced vasorelaxation of isolated thoracic aorta and have vascoluprotective effect in nitric oxide (NO) impaired rats. No liver or kidney toxicity was found in this study. Non-compartment pharmacokinetic analysis showed that the time to reach maximum concentration (Tmax) of plasma piperine after administration of piperine and STF were 3.9 and 1.7h, respectively. This result suggested that piperine in the recipe had better absorption than the pure standard piperine. ConclusionsSTF had no effect on blood pressure in both SHR and NWR. However, it was able to relax isolated thoracic aorta and had the potential for vasculoprotective effect in hypertensive and NO impaired condition. The effects of STF were comparable to those of piperine.

Pharmacokinetic Interaction between Magnolol and Piperine in Rats

Purpose: To investigate the pharmacokinetic mechanism of interaction between magnolol and piperine when co-administered to rats. Methods: The rats were divided into five groups as follows: magnolol group (625 mg/kg); low dose of piperine group (20 mg/kg); high dose of piperine group (40 mg/kg); low dose of piperine + magnolol group; or high dose of piperine + magnolol group. Plasma samples were collected at regular time intervals after administration of a single dose of magnolol (625 mg/kg, p.o.) alone or piperine (20 or 40 mg/kg, p.o.) in the presence or absence of magnolol (625 mg/kg, p.o.). The concentrations of magnolol and piperine in plasma were measured by a validated high performance liquid chromatography (HPLC) method. Results: Compared with control, the groups given magnolol alone, concomitant administration of piperine and magnolol resulted in significant decrease (p 0.05) alter the pharmacokinetic parameters of piperine. However, at high dose (40 mg/kg) of piperine, C max of piperine significantly decreased from 4.30 ± 1.47 to 2.50 ± 0.78 μg/mL (p < 0.05). Conclusion: Co-administration of magnolol and piperine decreases plasma concentration of either drug in rats, suggesting that concurrent use of magnolol with piperine or piperine-containing diets would require close monitoring for potential interactions. Keywords: Magnolol, Piperine, Pharmacokinetic interaction, Co administration

Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers

Piperine is the principal alkaloid in black peppers (Piper nigrum L.), which is a commonly included spice in anti-diarrheal formulations. Piperine has antispasmodic activities, but its anti-secretory effect is not known. Therefore, this study investigated the anti-secretory effect of piperine and its underlying mechanism. Piperine inhibited cAMP-mediated Cl− secretion in human intestinal epithelial (T84) cells, similar to black pepper extract. Intraluminal administration of piperine (2μg/loop) suppressed cholera toxin-induced intestinal fluid accumulation by ∼85% in mice. The anti-secretory mechanism of piperine was investigated by evaluating its effects on the activity of transport proteins involved in cAMP-mediated Cl− secretion. Notably, piperine inhibited CFTR Cl− channel activity (IC50#8’6#10μM) without affecting intracellular cAMP levels. The mechanisms of piperine-induced CFTR inhibition did not involve MRP4-mediated cAMP efflux, AMPK or TRPV1. Piperine also inhibited cAMP-activated basolateral K+ channels, but it had no effect on Na+–K+–Cl− cotransporters or Na+–K+ ATPases. Piperine suppressed Ca2+-activated Cl− channels (CaCC) without affecting intracellular Ca2+ concentrations or Ca2+-activated basolateral K+ channels. Collectively, this study indicates that the anti-secretory effect of piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K+ channels. Piperine represents a novel class of drug candidates for the treatment of diarrheal diseases caused by the intestinal hypersecretion of Cl−.

Effect of piperine on liver function of CF-1 albino mice.

Piperine is isolated from Piper nigrum popularly known as black pepper. Previous studies have demonstrated the beneficial effects of piperine in various health conditions. Additionally, it is a powerful bioenhancer for many drugs. Piperine extract is believed to potentiate the effect of drugs by several folds. The present study is focused on its individual effect on liver function. A total of 30 CF-1 albino mice obtained from the animal house of faculty of Medicine, Benghazi University, Benghazi, Libya were included in the study. These mice were fed with high cholesterol diet and divided into 2 groups. Twenty mice were administered piperine at a dose of 5mg/kg body weight. Piperine was isolated in Department of Pharmacognosy, Faculty of Pharmacy, Benghazi University, Benghazi and 10 mice were not administered piperine but fed with high fat diet. These mice were anesthetized with ketamine and halothane and blood was drawn from each mouse before the study and after three weeks by cardiocentesis. Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase and total protein were measured by authenticated methods. Serum alanine amino transferase was significantly elevated (p=0.0002) in group A mice after the administration of Piperine extract for three weeks compared to those of group B mice. Serum aspartate amino transferase was elevated significantly (p=0.046) and alkaline phosphatase (p= 0.0001) also was significantly increased after the administration of piperine. Serum total protein (p= 0.011) values were significantly decreased after the use of piperine for three weeks in group A mice. This study showed that there might have been a considerable damage to liver with piperine extract. Further research may be required to prove this damage to liver function.

English

Cognitive impairment in epileptics may be a consequence of the epileptogenic process as well as antiepileptic medication. Thus, there is need for drugs, which can suppress epileptogenesis as well as prevent cognitive impairment. In the present study, the effect of piperine was evaluated on the course of pentylenetetrazole (PTZ) induced seizures, learning deficit and oxidative stress `markers in mice. Male albino mice were injected with PTZ (65 mg/kg sc) on the 5th day of the treatment for the development of seizures. Spontaneous alternation behaviour was carried out on the 1st and the 5th day of the treatment after PTZ administration, while the oxidative stress parameters (malondialdehyde and glutathione) were carried out in the whole brain upon the completion of the behavioural assessment. The administration of piperine, 2 mg/kg significantly decreased the PTZ induced seizures and showed improvement in the learning deficit induced by PTZ as evidenced by the increased latency time and frequency of jerks and improvement in spontaneous alternation behavior (SAB). The findings suggest the potential of piperine as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment. Key words: Cognitive impairment, piperine, pentylenetetrazole.

Prevention of Pioglitazone Induced Weight Gain by Co Administration of Piperine

Prevention of Pioglitazone Induced Weight Gain by Co Administration of Piperine

Piperine inhibits the growth and motility of triple-negative breast cancer cells

Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells. Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells, without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression was decreased and p21Waf1/Cip1 expression was increased in piperine-treated TNBC cells. Piperine also inhibited survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may be useful in the treatment of TNBC.

Piperine potentiates the hypocholesterolemic effect of curcumin in rats fed on a high fat diet.

It has previously been demonstrated that curcumin possesses a hypocholesterolemic effect and potentiates numerous pharmacological effects of curcumin, however, the mechanisms underlying this hypocholesterolemic effect and the interaction between curcumin and piperine remain to be elucidated. In the present study, male Sprague-Dawley rats were fed on a high-fat diet (HFD) to establish a hyperlipidemia (HLP) model. Co-administration of curcumin plus piperine was found to decrease the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol in the serum and liver, as well as increase the levels of fecal TC, TG and total bile acid, compared with administration of curcumin alone. Curcumin plus piperine also markedly increased the levels of high-density lipoprotein cholesterol. Furthermore, compared with administration of curcumin alone, administration of curcumin plus piperine resulted in a significant upregulation of the activity and gene expression of apolipoprotein AI (ApoAI), lecithin cholesterol acyltransferase (LCAT), cholesterol 7α-hydroxylase (CYP7A1) and low-density lipoprotein receptor (LDLR). In conclusion, these results indicated that co-administration of curcumin plus piperine potentiates the hypocholesterolemic effects of curcumin by increasing the activity and gene expression of ApoAI, CYP7A1, LCAT and LDLR, providing a promising combination for the treatment of HLP.

Piperine and ketoconazole increase plasma domperidone concentrations in the rat (1064.2)

This study was carried out to investigate the effect of piperine, a major pungent constituent of the black and red peppers and ketoconazole on the pharmacokinetics of domperidone. Animals received a single dose of domperidone(20mg/kg, p.o.) alone or together with piperine (60mg/kg, p.o.) or ketoconazole(50 mg/kg, p.o.) daily for 5 days. Plasma samples were collected at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0 and 12h after drug administration. The concentrations of domperidone in the plasma were measured using an HPLC method. The concomitant administration of piperine or ketoconazole with domperidone resulted in a significant (p&lt;0.05) increase in the maximum plasma concentration(Cmax), the mean area under the plasma concentration‐ time curve(AUC), and the elimination half‐life(t1/2) of domperidone as compared to those obtained for domperidone alone. These results suggest that an important pharmacokinetic interaction may occur if piperine or ketoconazole are administered concurrently with domperidone.

Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis

ObjectivesPiperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. MethodsArthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg−1 and indomethacin at 1mgkg−1 body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1β, TNF-α, IL-10 and PGE2) and histological studies in joints. ResultsPiperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1β, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. ConclusionsIn conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.

Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice

This study examined the effect of piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13weeks and elucidated potential underlying molecular mechanisms. Administration of piperine (50mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered piperine. However, piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice. Administration of piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice.