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Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins

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Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.
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... Piperine (1) was isolated from the dried black pepper seed (Piper nigrum) powder on a modified extraction procedure [26,27]. Pure natural piperine was afforded at 6.43% yield based on the dry weight of the black pepper seed powder. ...
... The resulting solid was recrystallized in dichloromethane, which afforded 64.25 g of yellow crystalline piperine. This modified the extraction method [26,27], And yielded 6.43% piperine based on the dry weight of the dried Piper nigrum seed powder. IR (ATR, ...
Article
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Piper nigrum, or black pepper, produces piperine, an alkaloid that has diverse pharmacological activities. In this study, N-aryl amide piperine analogs were prepared by semi-synthesis involving the saponification of piperine (1) to yield piperic acid (2) followed by esterification to obtain compounds 3, 4, and 5. The compounds were examined for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. The new 2,5-dimethoxy-substituted phenyl piperamide 5 exhibited the most robust biological activities with no cytotoxicity against mammalian cell lines, Vero and Vero E6, as compared to the other compounds in this series. Its half-maximal inhibitory concentration (IC50) for antitrypanosomal activity against Trypanosoma brucei rhodesiense was 15.46 ± 3.09 μM, and its antimalarial activity against the 3D7 strain of Plasmodium falciparum was 24.55 ± 1.91 μM, which were fourfold and fivefold more potent, respectively, than the activities of piperine. Interestingly, compound 5 inhibited the activity of 3C-like main protease (3CLPro) toward anti-SARS-CoV-2 activity at the IC50 of 106.9 ± 1.2 μM, which was threefold more potent than the activity of rutin. Docking and molecular dynamic simulation indicated that the potential binding of 5 in the 3CLpro active site had the improved binding interaction and stability. Therefore, new aryl amide analogs of piperine 5 should be investigated further as a promising anti-infective agent against human African trypanosomiasis, malaria, and COVID-19.
... Similarly, addition of black pepper as food additive to broiler chicken diet resulted in lowering blood TG, TC, and LDL, while raising HDL levels (Puvača et al., 2015). In addition, it was reported that the ethanol extract of P. nigrum effectively inhibited cholesterol uptake in differentiated Caco-2 cells, suggesting that black pepper might prevent intestinal cholesterol absorption and subsequently reduce the serum TC levels (Duangjai, Ingkaninan, Praputbut, & Limpeanchob, 2013). The piperine-enriched extract was shown to reduce cholesterol transporter proteins (Niemann-Pick C1-like 1 (NPC1L1) and scavenger receptor class B type 1 (SR-B1)) expression in plasma membrane, which may be the mechanism by which black pepper reduced intestinal cholesterol absorption. ...
... Piperine also suppressed the expression of ATP-binding cassette transporters (ABC) G5/8 (ABCG5/8) and liver X receptor (LXR) in liver (Song et al., 2015), which is crucial for hepatobiliary and intestinal sterol excretion (Calpe-Berdiel et al., 2008). Piperine dose-dependently reduced cholesterol uptake into Caco-2 cells probably by reducing the membrane levels of the enterocyte carrier proteins, SR-B1 and Niemann-Pick C1-like 1 (NPC1L1) without changing total expression (Duangjai et al., 2013), indicating that piperine may prevent intestinal cholesterol absorption and further increase cholesterol excretion. ...
Article
Background Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Black pepper, the fruits of Piper nigrum L., is well known as “the king of spices” and used as seasoning and condiments globally. In addition to being an important food additive, black pepper is also used as a traditional medicine to treat vomiting, abdominal pain, and diarrhea, among others. Piperine is a major pungent alkaloid identified in the fruits of P. nigrum (black pepper), whose content is at a range of ~5–13%. Black pepper and piperine have shown protective effect on CVDs. Scope and approach Literature search was conducted to systematically review the cardiovascular protective effect of both black pepper and its major bioactive constituent piperine. Key findings and conclusions Black pepper was reported to regulate lipid metabolism, inflammation, and oxidation status in CVDs. Piperine exhibited beneficial effect by targeting many processes associated with atherosclerosis. Piperine is able to prevent lipid peroxidation, oxidized low-density lipoprotein uptake in macrophages, lipid droplet formation, and adhesion of inflammatory cells to endothelial monolayer, promote cholesterol efflux from macrophages, as well as improve lipid profile. Besides, piperine may ameliorate myocardial ischemia, cardiac injury, and cardiac fibrosis, exhibit antihypertensive and antithrombosis effect, as well as prevent arterial stenosis by inhibiting vascular smooth muscle cell proliferation. The summarized information could provide the basis to develop black pepper or piperine as a food additive to prevent or treat CVDs.
... It was extracted as a yellow crystalline compound with a melting point of 128 to 130 °C. The study of degradation of piperine, flavour of BP was widely studied for various applications in medical uses[65][66][67][68][69][70][71][72][73][74][75][76][77][78]. ...
... It enhances digestion process by helping faster break down of larger fat molecules into easily digestible simple molecules and prevents the accumulation of fat in body. Black pepper exhibits immunomodulatory effect on human body[69,77,151,152].Black and red pepper has been used for centuries as spice or food with healthful applications and suggest that dietary inclusion of peppers may attenuate some cardiometabolic risk markers associated to Western-style diet[153]. Piperaceae, a Latin name derived from Greek, which in turn originates from the Arabic word babary-black pepper, is considered one of the largest families of basal dicots, found in tropical and subtropical regions of both hemispheres. ...
Technical Report
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This article brings together an overview of the historical and scientific works on black pepper (BP). It's well known as the king of spices, and literature which is very rich showing that it was well cultivated tens of centuries ago before the birth of Christ. It was known first in India but its economic importance as well as medical uses extended to several countries. The ancient books illustrated the displacements of caravans of merchants known as route of Silks and Spices. Actually, the countries of India, Brazil, and Indonesia are the greatest commercial exporters. The major compound of black pepper is piperine that imparts pungency and biting taste to it. Hundreds of millions of results on black pepper on Google reflects the importance of this naturally occurring alkaloid. The numerous health effects and beneficial therapeutic properties have been largely demonstrated. The chemical composition of BP is so various to find heterocyclic components, and mineral ions as potassium, calcium, magnesium, iron … Advanced extraction and quick characterization yield these numerous alkaloids based on piperine. Also, the development of new formulations improves its in vivo bioavailability and explains the multiple uses of this "King" of spices in the medicinal applications. Black pepper and its isolated compounds served also as efficient corrosion of mild steel in acidic media
... It was extracted as a yellow crystalline compound with a melting point of 128 to 130 °C. The study of degradation of piperine, flavour of BP was widely studied for various applications in medical uses[65][66][67][68][69][70][71][72][73][74][75][76][77][78]. ...
... It enhances digestion process by helping faster break down of larger fat molecules into easily digestible simple molecules and prevents the accumulation of fat in body. Black pepper exhibits immunomodulatory effect on human body[69,77,151,152].Black and red pepper has been used for centuries as spice or food with healthful applications and suggest that dietary inclusion of peppers may attenuate some cardiometabolic risk markers associated to Western-style diet[153]. Piperaceae, a Latin name derived from Greek, which in turn originates from the Arabic word babary-black pepper, is considered one of the largest families of basal dicots, found in tropical and subtropical regions of both hemispheres. ...
Article
Full-text available
This article brings together an overview of the historical and scientific works on black pepper (BP). It's well known as the king of spices, and literature which is very rich showing that it was well cultivated tens of centuries ago before the birth of Christ. It was known first in India but its economic importance as well as medical uses extended to several countries. The ancient books illustrated the displacements of caravans of merchants known as route of Silks and Spices. Actually, the countries of India, Brazil, and Indonesia are the greatest commercial exporters. The major compound of black pepper is piperine that imparts pungency and biting taste to it. Hundreds of millions of results on black pepper on Google reflects the importance of this naturally occurring alkaloid. The numerous health effects and beneficial therapeutic properties have been largely demonstrated. The chemical composition of BP is so various to find heterocyclic components, and mineral ions as potassium, calcium, magnesium, iron … Advanced extraction and quick characterization yield these numerous alkaloids based on piperine. Also, the development of new formulations improves its in vivo bioavailability and explains the multiple uses of this "King" of spices in the medicinal applications. Black pepper and its isolated compounds served also as efficient corrosion of mild steel in acidic media
... Supplementation of black pepper to daily diet can promote absorption of nutrients and modulate lipid profile and obesogenic marker expression in high-fat-diet (HFD)-treated rats (Vijayakumar and Nalini, 2006). Duangjai et al., (2013) found piperine lowers blood lipids in vivo and inhibits cholesterol uptake in vitro. The mechanism of this effect was not due to the interference of either the size of lipid micelles or the cholesterol efflux pathway, nor changing of solubility of lipid micelles, but translocation of cholesterol transporter NPC1L1 and SR-BI proteins to the cytosol. ...
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Hyperlipidemia is associated with elevated cholesterol and triglyceride levels which is a risk factor for atherosclerosis. Spices being an integral part of culinary culture around the world are known to possess anti-cholesterol compounds and increase the high density lipoprotein cholesterol. This review presents a comprehensive scientific data on the anticholesterol/hypolipidemic activities of various spices used in traditional medicine and cuisine. Bioactive compounds from spices with anti-hyperlipidemic activities and their mode of action are summarized. The findings reaffirm the importance of spices by suggesting their anti-hyperlipdemic/anti-cholesterol activities to prevent cardiovascular diseases.
... Caco-2 cells as well as reduce plasma levels of TCL, LDL and VLDL. Translocation of cholesterol transporter NPC1L1 and SR-BI proteins to the cytosol is results in inhibition of cholesterol uptake (Duangjai et al, 2013). Black pepper significantly elevates the plasma HDL-cholesterol levels due to increased activity of lipoprotein lipase and lecithin cholesterol acyl transferace enzymes (Vijayakumar et al, 2002). ...
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Sri Lanka is a country where has efficacious food cultures related to their traditional life styles. In traditional food recipes native spices such as Garcinia cambogia or Garcinia zeylanica (Goraka or Malabar Tamarind), Tamarindus indica (Siyambala or Tamarind), Piper nigrum (Gammiris or Pepper), Trigonella foenum-graecum (Uluhal or fenugreek) and Cinnamomum zeylanicum (Kurundu or Cinnamon) are enriched. Recent advances in global perspectives on non-communicable diseases reconsidering traditional foods including spices for health prevention and promotion. Therefore, the current study aims to review ethnomedicinal value of aforementioned spices considering its biochemical effect on lipid profile including total cholesterols, triglycerides, low density lipoproteins and high density lipoproteins at cell biology and effect on biochemistry in cellular level. The study was designed as a literature review through primary and secondary literature sources which are available online with utmost attention to peer reviewed and indexed journal articles. Thirty articles were considered as references while reviewing fifty two related research studies. Biochemical modifications in cellular sites relevant to management of serum lipid values were identified in each of spices. Biochemical effect on lipogenesis and lipid metabolism in each variety were identified. The study suggests that the consumption of spices is beneficial in lipid level management.
... Caco-2 cells as well as reduce plasma levels of TCL, LDL and VLDL. Translocation of cholesterol transporter NPC1L1 and SR-BI proteins to the cytosol is results in inhibition of cholesterol uptake (Duangjai et al, 2013). Black pepper significantly elevates the plasma HDL-cholesterol levels due to increased activity of lipoprotein lipase and lecithin cholesterol acyl transferace enzymes (Vijayakumar et al, 2002). ...
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Full-text available
Sri Lanka is a country where has efficacious food cultures related to their traditional lifestyles. In traditional food recipes native spices such as Garcinia cambogia or Garcinia zeylanica (Goraka or Malabar Tamarind), Tamarindus indica (Siyambala or Tamarind), Piper nigrum (Gammiris or Pepper), Trigonella foenum-graecum (Uluhal or fenugreek) and Cinnamomum zeylanicum (Kurundu or Cinnamon) are enriched. Recent advances in global perspectives on non-communicable diseases reconsidering traditional foods including spices for health prevention and promotion. Therefore, the current study aims to review ethnomedicinal value of aforementioned spices considering its biochemical effect on lipid profile including total cholesterols, triglycerides, low-density lipoproteins, and high-density lipoproteins at cell biology and effect on biochemistry in the cellular level. The study was designed as a literature review through primary and secondary literature sources that are available online with utmost attention to peer-reviewed and indexed journal articles. Thirty articles were considered as references while reviewing fifty-two related research studies. Biochemical modifications in cellular sites relevant to the management of serum lipid values were identified in each of the spices. The biochemical effect on lipogenesis and lipid metabolism in each variety were identified. The study suggests that the consumption of spices is beneficial in lipid level management.
... 77 Black pepper extract has been considered in animals for its probable to trim down cholesterol levels. 26,78 It has been concluded that piperine can reduce cholesterol uptake by internalizing the cholesterol transporter proteins in high-fat diet-induced obesity in rats. 79 Black pepper does not contain cholesterol as one of its active chemical compound. ...
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Since ages, spices have been a crucial portion of human diets and trade. The bioactive principles in attendance are of noteworthy merit due to their advantageous probable against an array of disorders. Black pepper, amid piperine as its foremost element, holds affluent phytochemistry and also incorporates a number other important compounds like alkaloids, volatile oils and oleoresins. Piper nigrum is an imperative welfare spice owed to its anti-carcinogenic, antimicrobial, antioxidant apparent and gastro-defensive workings. Piperine also show evidence of speckled pharmacological characteristics like antidepressant, anti-inflammative, immunomodulatory, anticonvulsant, antihypertensive, antitumor, anti-tussive, pain reducing, antidiarrheal, antispasmodic, and cholesterol worsening . Piperine augments bioavailability of quite a few drugs and nutrients by restraining a variety of metabolising enzymes. This review is aimed to provide restructured information in recent progression of pharmacognosy, chemistry and pharmacological behavior of this miraculous King of Spices. Keywords: Black Pepper, Piperine, Antioxidant, Bioavailability, King of Spices
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Natural piperine from black pepper is known to function as hypocholesterolemic agent, but how it lowers the blood cholesterol remains unclear. In this study, we found that intragastric administrations of piperine (25 mg/kg/day) for 8 weeks significantly reduced the plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in high-fat diet (HFD)-fed mice. H&E staining indicated that piperine significantly decreased hepatic lipid accumulation compared with the control group. The Oil Red O staining further showed that piperine attenuated lipid deposition in liver HepG2 cells in a concentration-dependent manner. Mechanistically, piperine treatment caused a significant upregulation of hepatic scavenger receptor B1 (SR-B1) in the liver and transporter protein of ATP binding cassette SGM8 (ABCG8) in the small intestine. Taken together, our findings demonstrate the role of natural piperine in improving lipid metabolic profile that is involved in the reverse cholesterol transport (RCT)-mediated mechanism through upregulation of SR-B1 in the liver and ABCG8 in the small intestine.
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This study evaluated the chemical compositions of the leaves and fruits of eight black pepper cultivars cultivated in Pará State (Amazon, Brazil). Hydrodistillation and gas chromatography–mass spectrometry were employed to extract and analyze the volatile compounds, respectively. Sesquiterpene hydrocarbons were predominant (58.5–90.9%) in the cultivars “Cingapura”, “Equador”, “Guajarina”, “Iaçará”, and “Kottanadan”, and “Bragantina”, “Clonada”, and “Uthirankota” displayed oxygenated sesquiterpenoids (50.6–75.0%). The multivariate statistical analysis applied using volatile composition grouped the samples into four groups: γ-Elemene, curzerene, and δ-elemene (“Equador”/“Guajarina”, I); δ-elemene (“Iaçará”/“Kottanadan”/“Cingapura”, II); elemol (“Clonada”/“Uthirankota”, III) and α-muurolol, bicyclogermacrene, and cubebol (“Bragantina”, IV). The major compounds in all fruit samples were monoterpene hydrocarbons such as α-pinene, β-pinene, and limonene. Among the cultivar leaves, phenolics content (44.75–140.53 mg GAE·g−1 FW), the enzymatic activity of phenylalanine-ammonia lyase (20.19–57.22 µU·mL−1), and carotenoids (0.21–2.31 µg·mL−1) displayed significant variations. Due to black pepper’s susceptibility to Fusarium infection, a molecular docking analysis was carried out on Fusarium protein targets using each cultivar’s volatile components. F. oxysporum endoglucanase was identified as the preferential protein target of the compounds. These results can be used to identify chemical markers related to the susceptibility degree of black pepper cultivars to plant diseases prevalent in Pará State.
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Piperine {[1-5-(1, 3)-benzodioxol-5-yl)-1-oxo-2, 4-pentadienyl]-piperidine} ,an alkaloid responsible for the pungency of black pepper & long pepper. Systemic pharmacological studies on piperine have revealed that this compound elicited diverse pharmacological activities; analgesic, anti-pyretic, anti-inflammatory, anti-convulsant & CNS-depressant activities. Piperine was isolated from Piper nigrum Linn. (Piperaceae) and identified by TLC. Piperine was fabricated into alginate beads using sodium alignate. The main aim of this study was to demonstrate the sustained release of piperine from alginate beads by in vitro evaluation. The drug release studies were showed that the alginate beads sustained the release of the drug with % drug released in hours.
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Effect of administering black pepper (Piper nigrum Linn.), one of the commonly consumed spices and its active principle piperine, to high fat fed rats was studied for a period of 10 weeks. Black pepper at two different doses of 250 mg/kg body weight and 500 mg/kg body weight and piperine at 20 mg/kg body weight were made into a coarse solution with distilled water and administered orally by intragastric intubation daily. The plasma and tissue lipid profile showed a remarkable reduction in the levels of total cholesterol (both the free and ester cholesterol fractions), free fatty acids, phospholipids and triglycerides in black pepper as well as in the piperine treated groups. Moreover, supplementation of the high fat fed rats with black pepper or piperine elevated the concentration of high density lipoprotein-cholesterol and reduced the concentrations of low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol in the plasma as compared with the levels in unsupplemented high fat fed rats. Thus dietary intake of black pepper or piperine was found to reduce the risk of atherosclerosis markedly by virtue of its hypolipidemic and antiatherogenic effects.
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The secondary metabolites isolated from Piper species for the period 1907 to June 1996 have been reviewed. Nearly six hundred chemical constituents belonging to different classes of bioactive compounds are listed together with their source(s) and references. © 1997 Elsevier Science Ltd
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