Article

Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation

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Abstract

An extract from the fruits of black pepper consisting of a minimum of 98% pure piperine was evaluated in a clinical study using a double-blind design. The relative bioavailability of 90 mg and 120 mg of coenzyme Q10 administered in a single-dose experiment or in separate experiments for 14 and 21 days with placebo or with 5 mg of piperine was determined by comparing measured changes in plasma concentration. The inter-subject variability was minimized by limiting the selection of individuals to healthy adult male volunteers with (presupplementation) fasting coenzyme Q10 values between 0.30 and 0.60 mg/L. The results of the single-dose study and the 14-day study indicate smaller, but not significant, increases in plasma concentrations of coenzyme Q10 in the control group compared with the group receiving coenzyme Q10 with a supplement of piperine. Supplementation of 120 mg coenzyme Q10 with piperine for 21 days produced a statistically significant (p = 0.0348), approximately 30% greater, area under the plasma curve than was observed during supplementation with coenzyme Q10 plus placebo. It is postulated that the bioenhancing mechanism of piperine to increase plasma levels of supplemental coenzyme Q10 is nonspecific and possibly based on its description in the literature as a thermonutrient.

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... Previously it has been found that supplementation of coenzyme Q10 with an additional 5 mg of Bioperine® increased plasma levels of coenzyme Q10 more so than supplementation with coenzyme Q10 alone (Badmaev, Majeed, & Prakash, 2000). The increase in plasma levels of coenzyme Q10 observed in the study conducted by Badmaev et al. (2000) could indicate that Bioperine® supplementation may increase the bioavailability of other nutrients. ...
... Previously it has been found that supplementation of coenzyme Q10 with an additional 5 mg of Bioperine® increased plasma levels of coenzyme Q10 more so than supplementation with coenzyme Q10 alone (Badmaev, Majeed, & Prakash, 2000). The increase in plasma levels of coenzyme Q10 observed in the study conducted by Badmaev et al. (2000) could indicate that Bioperine® supplementation may increase the bioavailability of other nutrients. ...
Article
Purpose: The purpose of this study was to investigate the acute effect of Myosync™ on physical performance in Division II football players. Methods: Fourteen male Division II football players (20.4 ± 1.0 years) participated in a randomized double blind crossover experiment. Subjects were either given Myosync™ or a placebo control 60 minutes prior to any physical testing measures. Testing consisted of, maximum vertical jumps, maximum voluntary isometric contractions (MVIC), maximal voluntary concentric contractions (MVCC), and fatiguing contractions for the knee extensor muscles. Recovery measures consisted of one MVIC and MVCCs 10 minutes after fatiguing task. Results: There was no difference in maximum vertical jump height between control and supplemental sessions (P = 0.90). MVIC was similar between control and supplemental sessions at baseline (P = 0.34). Rate of torque development was significantly higher throughout the fatiguing task during the supplemental session (P = 0.02). Impulse for all MVIC significantly increased at 200 ms throughout the fatiguing task during the supplemental session (P < 0.001). Conclusion: Maximal strength, power and vertical jump did not improve with Myosync™, however, the significant increases in rate of torque development and impulse could be beneficial for a variety of athletes.
... For midazolam (sedative), prolonged and increased pharmacological effects of the drug (prolonged duration of sedation, increased number of individuals with amnesia) were observed with piperine administration of 15 mg/day for 3 days and subsequent midazolam administration on the 4th day [78]. For the substances β-carotene and coenzyme Q10, increased bioavailability was already observed in the case of combined administration of 5 mg piperine/day with 15 mg β-carotene/day for 14 days or with 120 mg coenzyme Q10/day, respectively, for 21 days [123,124]. Regarding curcumin, the Cmax or AUC values were approx. 30 or 20 times higher, respectively, when administered together with 20 mg piperine/day [125]. ...
... Concerning the improved bioavailability seen with several drugs, different underlying mechanisms have been discussed, such as improved drug absorption and/or inhibition of degradation or elimination. In this context, depending on the drug or investigated substance, different mechanisms for influencing absorption and different molecular targets relating to the metabolism of xenobiotics are at the center of discussion, viz. the unspecific gastrointestinal effects (increased splanchnic blood flow), altered membrane dynamics, inhibition of cytochrome P-450 enzymes (CYP3A4, CYP2E1, CYP2C9, etc.), inhibition of multispecific efflux transporters, such as P-glycoprotein, or other mechanisms [1,15,[73][74][75][76][77][78]120,124,150]. ...
Article
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Piperine is a natural ingredient of Piper nigrum (black pepper) and some other Piper species. Compared to the use of pepper for food seasoning, piperine is used in food supplements in an isolated, concentrated form and ingested as a bolus. The present review focuses on the assessment of the possible critical health effects regarding the use of isolated piperine as a single ingredient in food supplements. In human and animal studies with single or short-term bolus application of isolated piperine, interactions with several drugs, in most cases resulting in increased drug bioavailability, were observed. Depending on the drug and extent of the interaction, such interactions may carry the risk of unintended deleteriously increased or adverse drug effects. Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis and of maternal reproductive and embryotoxic effects. Although the available human studies rarely reported effects that were regarded as being adverse, their suitability for detailed risk assessment is limited due to an insufficient focus on safety parameters apart from drug interactions, as well as due to the lack of investigation of the potentially adverse effects observed in animal studies and/or combined administration of piperine with other substances. Taken together, it appears advisable to consider the potential health risks related to intake of isolated piperine in bolus form, e.g., when using certain food supplements.
... Research on piperine from Black pepper given as oral supplementation has shown increase in plasma levels of coenzyme Q10. 56 Serum level of β-Carotene has been found to be increased by piperine, thus to overcome vitamin deficiency piperine enhanced β-Carotene uptake can be ISSN: 2250-1177 ...
... The pharmacokinetic profile of a number of synthetic drugs like omeprazole, propranolol, ampicllin, norfloxacin ciprofloxacin, amoxicillin, isoniazid, theophylline and phenytoin has been influenced or improved by piperine. 56,60,65 Promising results have also been evident in plentiful other other pharmaceutically active chemicals like nevirapine, diclofenac, midazolam, tamoxifen, carbamazepine to name a few. [66][67][68] Piperine has also found to affect enzyme commotion and biotransformation. ...
Article
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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
... Piperine (1-piperoyl piperidine), a major alkaloid from black pepper, has been shown to enhance permeation and bioavailability of various active compounds, administered orally [29,42,43]. It has been proposed that piperine increases membrane fluidity and modulates membrane dynamics, possibly by interacting with surrounding lipids and hydrophobic portions in the protein vicinity [42,43]. ...
... Piperine (1-piperoyl piperidine), a major alkaloid from black pepper, has been shown to enhance permeation and bioavailability of various active compounds, administered orally [29,42,43]. It has been proposed that piperine increases membrane fluidity and modulates membrane dynamics, possibly by interacting with surrounding lipids and hydrophobic portions in the protein vicinity [42,43]. A trace amount of 0.035 mM of piperine, introduced into the liposome formulation slightly increased zeta potentials and affected particle morphology of nanosized quercetin liposomes, and enhanced cell permeation by alteration of membrane dynamics. ...
... Piperine [(E,E)-5-(3,4-Methylenedioxyphenyl)-2,4-pentadienoylpiperidide, 1-Piperoylpiperidine] is an alkaloid in the nonvanilloid family, which occurs in berries and roots of the Piperaceae family (Badmaev et al., 2000;Vasavirama and Upender, 2014). Depending on the source, piperine content in berries varies from about 60 to 100 g/kg. ...
... Since curcumin combined with piperine produces much higher positive results, the accuracy of this assumption for honeybees should be checked. Piperine can also operate as a factor increasing the bioavailability of CoQ10 in human plasma in oral administration (Badmaev et al., 2000). In another publication, Strachecka et al. (2014b) also indicated that CoQ10 has an unexpectedly strong positive impact on honey bee health. ...
Article
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Many factors, including pathogens, environmental change and breeding techniques, affect honeybee immunity/resistance, so substances and natural supplements that enhance it are desired. To eliminate the impact of unknown external factors, in 2016 a cage experiment was conducted under constant laboratory conditions (35 °C, 65% relative humidity). Bees in the control group were fed with sugar dissolved in water at ratio 1:1 ad libitum with no additives, while the other group was fed with sugar syrup (1:1) supplemented with piperine (3 µg/ml) ad libitum . The piperine-treated workers lived 9 days longer compared to the control group. In the piperine-consuming group, protein concentration and the activities of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione S-transferase (GST), were higher than in the control group. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were also higher in the piperine-treated group. Neutral and acidic proteases inhibitors, as well as neutral protease activities, were higher in the haemolymph of the piperine-treated workers than in untreated bees. Acidic protease activities in the haemolymph were higher in untreated workers only on days 18 and 32. Alkaline protease activities in the control bees were higher from day 10. From 10 days old, the total antioxidant capacity level was significantly higher in the haemolymph of piperine-treated workers. Piperine decreased DNA methylation levels significantly in the older bees. The compound could have the potential to be a natural diet supplement increasing apian resistance to stress factors.
... Piperine increases the bioavailability of the coenzyme Q10 in plasma in a nonspecific fashion when orally administered [138]. The pharmacokinetics of ciprofloxacin changed when piperine was co-administered, emphasizing the fact that it acts as bioenhancer [139]. ...
... Also, it was found that when piperine was combined with β-carotene, a significantly greater increase (60% greater AUC) in serum β-carotene occurred during oral supplementation with these two compounds [158]. The same authors [138] found that piperine supplementation may result in improved absorption of coenzyme Q10, but also demonstrated that this effect has dose and time dependency. Another natural compound, phytoalexin resveratrol, has been reported to be more bioavailable when co-supplemented with piperine. ...
Article
Piperine is the main compound present in black pepper, and is the carrier of its specific pungent taste, which is responsible for centuries of human dietary utilization and worldwide popularity as a food ingredient. Along with the application as a food ingredient and food preservative, it is used in traditional medicine for many purposes, which has in most cases been justified by modern scientific studies on its biological effects. It has been confirmed that piperine has many bioactive effects, such as antimicrobial action, as well as many physiological effects that can contribute to general human health, including immunomodulatory, hepatoprotective, antioxidant, antimetastatic, antitumor, and many other activities. Clinical studies demonstrated remarkable antioxidant, antitumor, and drug availability-enhancing characteristics of this compound, together with immunomodulatory potential. All these facts point to the therapeutic potential of piperine and the need to incorporate this compound into general health-enhancing medical formulations, as well as into those that would be used as adjunctive therapy in order to enhance the bioavailability of various (chemo)therapeutic drugs.
... Which may involve micelle formation, hyperemia, epithelial cell wall modification or may be due to thermogenic properties of piperine [128]. When 98% of the piperine (5 mg/kg) extracted from the fruits of black pepper was used in double blinded clinical study increased the rate of absorption and bioavailability of coenzyme Q10 at the doses of 90 mg and 120 mg for 14 days and 20 days, but the exact mechanism underlying this effect is not clear [129]. Velapandian et al, 2001 conducted a pharmacokinetic study to explore the effect of piperine containing food on phenytoin (10 mg). ...
Article
Natural products, especially foods and extracts from plant origin have been successful in treating various disorders in traditional medicine. Piperine, a versatile bioactive compound is found in almost 2000 varieties of piper species from piper genus. The plants containing piperine, particularly, Piper nigrum (black pepper) and Piper longum (long pepper), are widely used in the traditional as well as alternative therapies for both human and domestic illnesses. Effect of piperine on gastrointestinal system, drug metabolizing enzymes, P-glycoprotein and alteration of bioavailability of other drugs are the major area of research. Particularly, bio-enhancing properties of piperine is of clinical importance, as co-administration with drugs for the treatment of human immunodeficiency virus (HIV) infections, pancreatitis, tuberculosis, hyperlipidemia, bronchial asthma and epileptic disorders, resulted in enhanced bioavailability of these drugs. Also investigations are being carried out to elucidate the underlying mechanism of action for the anti-fertility and anti-cancer effects of piperine. Comprehensive data regarding the in silico, safety, pre-clinical pharmacology, clinical studies of piperine and its derivatives are compiled in this review, to act as a guide for future drug development.
... Similarly, Piperine had been used along with a number of drugs because of its bioenhancing effects. Examples include Piperine and Aflatoxin B [13], Piperine and Phenytoin [14], Piperine and Pentobarbitone [15], Piperine and Curcumin [16], Piperine and β-Carotene [17], Piperine and Coenzyme Q10 [18], Piperine and Resveratrol [19] are evident from literature. Lysergol, a phytomolecule, is obtained from Morning Glory Plant (Ipomoea spp.) which enhances the killing activities of different antibiotics on bacteria and is a promising herbal bioenhancer. ...
... This bioenhancing effect was attributed to inhibiting glucuronidation, and slowing down the elimination of resveratrol by piperine [98]. Moreover, earlier human studies demonstrated that oral supplementation of piperine increased gastrointestinal absorption of beta carotene [99] and elevated plasma levels of co-enzyme Q10 [100]. ...
Article
Background Many of the activities associated with pepper fruits have been attributed to piperine, the most active compound present in these spices. Objective This paper aims to provide an overview of the known properties of piperine, i.e. piperine’s chemistry, its physiological activity, documented interactions as a bioenhancer and reported data concerning its toxicity, antioxidant properties and anticancer activity. Discussion It is known that piperine possesses several properties. In its interaction with other drugs, it can act as a bioavailability enhancer; this effect is also manifested in combination with other nutraceuticals, e.g. with curcumin, i.e. piperine can modify curcumin’s antioxidant, anti-inflammatory, antimicrobial and anticancer effects. Piperine displays significant immunomodulating, antioxidant, chemopreventive and anticancer activity; these effects have been shown to be dose-dependent and tissue-specific. However, the main limitation associated with piperine seems to be its low bioavailability, a disadvantage that innovative formulations are overcoming. Conclusion It is predicted that an increasing number of studies will focus on piperine, especially those directed towards unraveling its properties at the molecular level. The current knowledge about the action of piperine will form a foundation for ways to improve piperine’s bioavailability e.g. exploitation of different carrier systems. Only then will the therapeutical applications of this compound become clarified, and piperine will be recognized as an important nutraceutical.
... Piperine is part of a group of compounds known as "Vanilloids," because they are identified by the existence of a functional group depend on the structure of vanillin. Piperine is a natural substance present as the principal pungent component (1-9 %) in several portions of a plant which belong to the Piperaceae family [14] . Piperine, the most enormous alkaloid in pepper, was first identified by Hans Christian Ørsted from the pepper extract in 1819. ...
... Black peppe (piperine) Increased gastrointestinal absorption of the coenzyme Q10. Badmaev et al. 2000 Dill (seed extracts) Exhibited mucosal protective and antisecretory effects of the gastric mucosa in mice. Hosseinzadeh et al. 2002 Fennel (seed oil emulsion) Was superior to placebo in decreasing intensity of infantile colic. ...
Article
Full-text available
Spices have broadly been used as food flavoring and folk medicine since ancient times. Numerous phytochemicals have been identified in spices, namely thymol (ajowan and thyme), anethole (aniseed), piperine (black pepper), capsaicin (capsicum), cinnamaldehyde (cinnamon), eugenol (clove), linalool (coriander), sabinene (curry leaf), limonene (dill seed), estragole (fennel seed), allicin (garlic), gingerol (ginger), safranal (saffron), and curcumin (turmeric), among others. The antioxidants in spices are very effective and also render anti-mutagenic, cardioprotective, anti-inflammatory, and anti-cancer properties. Apart from their antioxidant efficacy, spices, particularly their essential oils possess strong antimicrobial activity against bacteria, fungi, yeasts, and microbial toxins synthesis. In this contribution, a summary of the most relevant and recent findings on phytochemical composition and antioxidant properties of spices has been compiled and discussed. The content of phenolic acids, flavonoids, tannins, glycosides, steroids, and terpenoids in different spices are summarized. In addition, the beneficial effects of spices in food preservation and in health promotion and disease risk reduction are briefly described.
... Clinical studies have shown the effect of piperine to increase plasma levels of pharmaceutical drugs and bioactive phytochemicals in humans including other substances, e.g. the antiretroviral drug nevirapine against HIV-1 infection and AIDS (Kasibhatta and Naidu, 2007), β-blocker propranolol and asthma drug theophylline (Bano et al., 1991), the antiepileptic drug phenytoin (Velpandian et al., 2001), the antiinflammatory phytochemical curcumin (Shoba et al., 1998) and coenzyme Q10 (Badmaev et al., 2000). The latter is the only long-term study (21 days) which tested the bioavailability of this nutritional compound based on a continuous and concurrent daily ingestion with piperine at levels of 5 mg/kg bw per day. ...
... Black peppe (piperine) Increased gastrointestinal absorption of the coenzyme Q10. Badmaev et al. 2000 Dill (seed extracts) Exhibited mucosal protective and antisecretory effects of the gastric mucosa in mice. Hosseinzadeh et al. 2002 Fennel (seed oil emulsion) Was superior to placebo in decreasing intensity of infantile colic. ...
Article
Full-text available
Spices have broadly been used as food flavoring and folk medicine since ancient times. Numerous phytochemicals have been identified in spices, namely thymol (ajowan and thyme), anethole (aniseed), piperine (black pepper), capsaicin (capsicum), cinnamaldehyde (cinnamon), eugenol (clove), linalool (coriander), sabinene (curry leaf), limonene (dill seed), estragole (fennel seed), allicin (garlic), gingerol (ginger), safranal (saffron), and curcumin (turmeric), among others. The antioxidants in spices are very effective and also render anti-mutagenic, cardioprotective, anti-inflammatory, and anti-cancer properties. Apart from their antioxidant efficacy, spices, particularly their essential oils possess strong antimicrobial activity against bacteria, fungi, yeasts, and microbial toxins synthesis. In this contribution, a summary of the most relevant and recent findings on phytochemical composition and antioxidant properties of spices has been compiled and discussed. The content of phenolic acids, flavonoids, tannins, glycosides, steroids, and terpenoids in different spices are summarized. In addition, the beneficial effects of spices in food preservation and in health promotion and disease risk reduction are briefly described.
... Piperineis an alkaloid responsible for the pungency of black pepper and long pepper, along with chavicine (Fig 1). It has also been used in some forms of traditional medicine [15][16][17][18][19][20]. Piperine has been shown to enhance the bioavailability of structurally and therapeutically diverse drugs [21]. ...
... Similarly supplementation of 120 mg coenzyme Q10 with piperine for 21 d produced a statistically significant (P = 0.0348) and approximately 30% greater, area under the plasma curve than was observed during supplementation with coenzyme Q10 plus placebo. It was postulated that the bio-enhancing mechanism of piperine to increase plasma levels of supplemental coenzyme Q10 is non-specific and possibly based on its description in the literature as a thermonutrient 95 . Gupta et al., illustrated that piperine at a dose of 10 mg/kg significantly increased the analgesic activity of nimesulide administered at a submaximal dose of 6.5 mg/kg of body weight. ...
Article
Herbal sources have been explored recently at very high frequency owing to their lower risk benefit ratio as compared to the modern allopathic medicine systems. Herbal bioenhancer is an agent of herbal origin or any phytomolecule, which is capable of enhancing bioavailability and bioefficacy of a particular drug or nutrient with which it is combined, without any typical pharmacological activity of its own at the dose used. The active compound of both Long pepper (Piper longum) and Black pepper (Piper nigrum) is piperine (1-piperoyl piperidine), which is responsible for bioenhancing effect. Piperine enhances absorption from gastrointestinal tract by various mechanisms and reduces gut metabolism of drugs. Piperine modulates membrane dynamics and lipid environment and increases permeability at site of absorption. Thus, piperine acts as absorption enhancer and is a potent inhibitor of drug metabolism as it inhibits various metabolizing enzymes like human p-glycoproteins, CYP3A4, UDP-glucose dehydrogenase (UDP-GDH), aryl hydrocarbon hydroxylase (AAH) and UDP-glucuronyl transferase. The current review also describes the mechanism of action of piperine and bioavailability action of piperine on drugs and nutrients.
... [17] Some of the scientifically documented drugs, which are affected by "piperine" co-administration are cited in Table 1. [7,[18][19][20][21][22][23][24][25][26] ...
Article
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The concept of bioavailability enhancer is new to the modern system of medicine. Basically, this concept originated in Ayurveda and being used in this system of medicine since centuries. Bio-enhancers augment the bioavailability or biological activity of drugs when co-administered with principal drug at low doses. Ayurveda is using several drugs such as Piper longum Linn., Zingiber officinale Rosc., and Glycyrhhiza glabra Linn. as bio-enhancers and different methods for bio-enhancing since centuries. The bio-enhancement leads to reduction in therapeutic dose of principal drug, thus reducing the possibilities of toxicity and side effects of drug, potentiating the efficacy, reducing the resistance, decreasing the requirement of raw material for drug manufacture, and ultimately benefitting to the world economy by reducing the treatment cost. This review article attempts to consolidate different drugs as well as methods being used traditionally for enhancing bioavailability in Ayurvedic system of medicine and to discuss their possible mechanism of action. Authentic subject material has been reviewed from different Ayurvedic texts and from different related research and review articles. Thus, it is a humble effort to explore the different aspects of bio-enhancers including therapeutic techniques such as Shodhana, the drugs such as Pippali, and properties such as Yogavahi and Rasayana, which have been described in Ayurveda along with their mechanism of action and uses wherever available.
... Piperine inhibits gastric emptying and transit time [26] which may delay the secretion of anorectic gut peptides, and hence delay their appearance in plasma. It is therefore possible that serial gut peptide measurement or visual analogue scales would have afforded a greater understanding of the satiating impact of BP. ...
Article
Background: Thermogenic ingredients may play a role in weight management. In vitro and rodent work suggests that components of black pepper may impact energy expenditure, and in humans, other TPRV1 agonists e.g. capsaicin, augment EE. Objectives: To determine the impact of BP on 24-hour EE, respiratory quotient, and biochemical markers of metabolism and satiety, a randomized, controlled, cross-over study of black pepper (0.5mg/meal) versus no pepper control was conducted in post-menopausal women. Subjects spent two 24-hour periods in a whole room indirect calorimeter. Results: Post-meal glucose, insulin, gut peptides and catecholamines were measured. Energy expenditure, respiratory quotient, or biochemical markers assessed did not differ significantly between the black pepper and no pepper control study days. Conclusions: Our findings do not support a role for black pepper in modulating energy expenditure in overweight postmenopausal women. Future work targeting alternative populations, administering black pepper in the fasted state, or in combination with other spices, may reveal the thermogenic effect of this spice. Trial registration: This trial was registered at clinicaltrials.gov (NCT01729143). Key words: Black pepper, piperine, energy expenditure, metabolic chamber
... In so doing it interferes with the signalling mechanisms between cancer cells, thereby reducing the chances of tumour progression. Collectively, these properties make black pepper one of the most important spices for preventing cancer(Vladimir et al., 2000). An extract from the fruits of black pepper consisting of a minimum of 98% pure piperine was evaluated in a clinical study using a double-blind design. ...
Article
Full-text available
Novel study to focus on actual experimental results for cancer percentage disease between India and Denmark countries to initiate a new idea to make a comparison between all effects of cancer disease to reach to very important factor and this factor is food quality from olive, onion, lemon, garlic, ginger, flavor, tomato and meat to produce a new mathematical model with a new idea that represents this disease as a chemical reaction passes in five phases each phase has it is own properties to make optimization by using SQP method to reach to the optimum concentration of food to reduce cancer percentage more than 97% and improve all these results theoretically.
... Similarly, Piperine had been used along with a number of drugs because of its bioenhancing effects. Examples include Piperine and Aflatoxin B [13], Piperine and Phenytoin [14], Piperine and Pentobarbitone [15], Piperine and Curcumin [16], Piperine and β-Carotene [17], Piperine and Coenzyme Q10 [18], Piperine and Resveratrol [19] are evident from literature. Lysergol, a phytomolecule, is obtained from Morning Glory Plant (Ipomoea spp.) which enhances the killing activities of different antibiotics on bacteria and is a promising herbal bioenhancer. ...
Article
Background: Silymarin, a widely used hepatoprotective drug, exhibits low oral bioavailability mainly because of poor water solubility, poor absorption, rapid metabolism and ultimately poor oral bioavailability of silymarin. Objective: Therefore, the present study was aimed to investigate the effects of Piperine, Fulvic acid and Lysergol as bioenhancers on the intestinal absorption of silymarin. Method: Non-everted sacs of rat small intestines were incubated in tyrode buffer solution which contained Silymarin in the absence or presence of various bioenhancers viz. Piperine, Fulvic acid and Lysergol alone and in combinations with each other in different concentrations. Result: It was found that Silymarin alone had apparent permeability coefficient Papp x 10-6 cm/s value of 1.63 and human fraction absorbed Fa (%) value of 21% as compared to which the highest values Papp x 10-6 cm/s 7.01 and Fa (%) > 100% were found to be for Silymarin- Fulvic acid (1:1) mixture + Piperine (10%). The absorption transport of Silymarin was significantly enhanced in the presence of Piperine and Fulvic acid, suggesting that the Piperine acted as hepatic and intestinal glucoronidation inhibitor of Silymarin and Fulvic acid increased the water solubility of Silymarin and aided in the transport of Silymarin across the intestinal epithelial cells. However, the addition of Lysergol at various concentrations (1%, 5% and 10%) had no significant effect on Silymarin transport. Conclusion: The results of the study suggest that the use of such effective bioenhancers in Silymarin formulations may enhance the oral absorption and hence the oral bioavailability of Silymarin.
... In a human clinical study, oral administration of piperine has been shown to increase the swallow response of patients with oropharyngeal dysphagia (Rofes et al., 2014). Randomized clinical trials involving humans subjected to oral administration of piperine have been reported for the treatment of diverse diseases, and none of them have stated that piperine is toxic to neither animals nor humans (Badmaev et al., 2000;Volak et al., 2013;Panahi et al., 2017). Piperine has been evaluated for its immunomodulatory effect and reported to increase the total WBC count, bone marrow cellularity, etc. (Sunila and Kuttan, 2004;Pathak and Khandelwal, 2009). ...
Article
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Candida albicans is the primary etiological agent associated with the pathogenesis of candidiasis. Unrestricted growth of C. albicans in the oral cavity may lead to oral candidiasis, which can progress to systemic infections in worst scenarios. Biofilm of C. albicans encompasses yeast and hyphal forms, where hyphal formation and yeast to hyphal morphological transitions are contemplated as the key virulence elements. Current clinical repercussions necessitate the identification of therapeutic agent that can limit the biofilm formation and escalating the susceptibility of C. albicans to immune system and conventional antifungals. In the present study, a plant-derived alkaloid molecule, piperine, was investigated for the antibiofilm and antihyphal activities against C. albicans. Piperine demonstrated a concentration-dependent antibiofilm activity without exerting negative impact on growth and metabolic activity. Inhibition in the hyphal development was witnessed through confocal laser-scanning microscopy and scanning electron microscopy. Interestingly, piperine displayed a tremendous potential to inhibit the virulence-associated colony morphologies, such as filamentation and wrinkling. Furthermore, piperine regulated morphological transitions between yeast and hyphal forms by inhibiting hyphal extension and swapping hyphal phase to yeast forms yet under filamentation-inducing circumstances. Remarkably, piperine-challenged C. albicans exhibited low potential for spontaneous antibiofilm resistance development. In addition, piperine effectively reduced in vivo colonization and prolonged survival of C. albicans-infected Caenorhabditis elegans, thereby expounding the distinct antivirulent potential. Transcriptomic analysis revealed piperine significantly downregulating the expression of several biofilm related and hyphal-specific genes (ALS3, HWP1, EFG1, CPH1, etc.). Furthermore, no acute toxicity was observed in the HBECs and nematodes exposed to piperine. Altogether, results from this study reveals the potential of piperine to inhibit biofilm and hyphal morphogenesis, and its in vivo efficacy and innocuous nature to HBECs suggests that piperine may be considered as a potential candidate for the treatment of biofilm-associated C. albicans infection, especially for oral candidiasis.
... In so doing it interferes with the signalling mechanisms between cancer cells, thereby reducing the chances of tumour progression. Collectively, these properties make black pepper one of the most important spices for preventing cancer(Vladimir et al., 2000). An extract from the fruits of black pepper consisting of a minimum of 98% pure piperine was evaluated in a clinical study using a double-blind design. ...
Article
Full-text available
Novel study to focus on actual experimental results for cancer percentage disease between India and Denmark countries to initiate a new idea to make a comparison between all effects of cancer disease to reach to very important factor and this factor is food quality from olive, onion, lemon, garlic, ginger, flavor, tomato and meat to produce a new mathematical model with a new idea that represents this disease as a chemical reaction passes in five phases each phase has it is own properties to make optimization by using SQP method to reach to the optimum concentration of food to reduce cancer percentage more than 97% and improve all these results theoretically.
... They concluded that the combination of piperine with curcumin showed quite significantpotentiation of its antiimmobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory effects as compared to curcumin effect [68]. Kulkarni [75]. Vladimir et al., 1999 studied the effect of simultaneous administration of piperine on serum concentration of β-carotene in healthy volunteers for 14-days. ...
Article
Bioenhancers are such agents, which by themselves are not therapeutic entities but when combined with an active drug lead to the potentiation of the pharmacologic effect of the drug. Such formulations have been found to increase the bioavailability / bioefficacy of a number of drugs even when reduced doses of drugs are present in such formulations. Evidence have been obtained for such classes of drugs which are (a) poorly bioavailable and/or efficacious, (b) require prolonged therapy, and (c) are highly toxic and expensive. These are phytomolecules development of which is based on ancient knowledge of Ayurveda. They augment the bioavailability or biological activity of drugs when administered at low doses. They reduce the dose; shorten the treatment period thus reducing drug-resistance problems. The treatment is made cost effective, minimizing drug toxicity and adverse reactions. When used in combination with number of drug classes such as antibiotics, antituberculosis, antiviral, antifungal and anticancerous drugs they are quite effective. Oral absorption of vitamins, minerals, herbal extracts, amino acids and other nutrients are improved by them. They act through several mechanisms which may affect mainly absorption process, drug metabolism or action on drug-target.
... The inter subject changes were diminished by careful selection of experimental volunteers to healthy men with coenzyme Q10 fasting values 0.30 and 0.60 mg/L, respectively. The resultant data of single and the 14 day trial showed lesser rise in coenzyme Q10 concentrations of plasma in control as compared to individuals getting coenzyme Q10 with piperine as a supplement (Badmaev et al., 2000). ...
Article
Contemporary nutrition regime has focused the attention of the researchers on phytochemi-cals enriched spices to mitigate various oncological threats. Numerous chemopreventive strategies against malignancy have been developed considering the anticancer perspectives of allied nutraceutical constituents. Current evidences have proven an inverse association of spices with that of oncological incidences. The high antioxidant activity of spices derived bi-oactives triggers the free radicals scavenging ability at cellular level thereby alleviating various metabolic syndromes. Promising compounds including curcumin and curcuminoids (turmeric), limonene (cardamom), allicin, allyl isothiocyanate (garlic), cinnamic aldehyde, 2-hydroxycinnamaldehyde and eugenol (cinnamon), gingerol, zingiberone, zingiberene (ginger), dipropyle disulfides and quercetin (onion), piperidine piperine, limonene, α- and β-pinene (black pepper), crocetin, crocin and safranal (saffron) have been identified as chemo-preventing agents against various malignancies. Chemopreventive properties of spices are mediated by functional bioactive ingredients that arrest the activity of cytochrome P450 and isozymes CYP 1A1, cyclooxygenase-2, reducing activator of transcription-3 (STAT-3) and signal transducer. They are closely associated with tumorigenesis activated by interleukin-6 (IL-6) receptors and epidermal growth factor (EGF) relate to an array of tumors. The bioac-tive constituents altering the expression of protein involved in cell cycle, activating caspases killer and suppressing Kappa-B activation. Alongside, they also restrain causative agents of cell structure damage as in lipid and protein membrane system and DNA that shifting healthy body towards cancerous state. Spices phytochemicals have established as carcinogenesis blockers by modulating cell proliferation pathways transformation, inflammation, metastasis etc. Furthermore, spices as functional ingredients may act as immune boosters and diminish inflammatory disorders. The current review is inevitably an affirmative approach in the development of novel guidelines against cancer by using dietary species to maintain good health.
... Black pepper has been added due to some evidence showing that it enhances absorption of supplements. 19,20 Huperzine-A is a lesser-known and not yet widely utilized ingredient. Huperzine-A, a compound extracted from plants, such as toothed clubmoss, is mostly researched acting as an acetylcholinesterase inhibitor, which increases the levels of the neurotransmitter acetylcholine. ...
Article
Purpose: The purpose of this pilot study was to assess the acute effects of consuming pre-workout supplements on indices of muscular strength, endurance and mood states. Methods: In a double- blind, placebo-controlled, randomized crossover design, fourteen moderate to highly-trained recreational athletes (7 female, 7 male) participated in this investigation. Subjects came to the lab twice between testing sessions. They consumed either pre supplement (mixed with 8 to 12 ounces of water) or placebo 30-minutes prior to testing. The pre-workout supplement combination (Athelite Nutrition Inc.) contained 15.62 grams per serving, 25 kcals, that consisted of a proprietary blend including caffeine (as green coffee bean extract), L-theanine, black pepper extract, micronized creatine monohydrate, CarnoSyn® beta-alanine, Huperzine A, N-Acetyl L-carnitine, Nitrosigine®), or placebo. The placebo was a similar tasting drink with an equal amount of caffeine. Their body composition was assessed via the DEXA (Hologic Model Horizon W). Participants’ mood was also assessed via a profile mood states questionnaire (POMS) 30 minutes after product or placebo was consumed. After taking the profile mood states questionnaire, subjects had their exercise performance assessed via the 1-repition maximum bench press followed by bench press repetitions to failure at 60% of 1-repetition maximum with 30 seconds rest between sets (3 total sets). Results: There were significant differences (p Conclusion: The results demonstrated that the acute consumption of pre-workout supplements can enhance muscular endurance. Caffeine alone cannot explain effect on muscular endurance since the placebo also contained caffeine. However, the supplements had no effect on strength or mood states.
... This suggests that a higher dose, or enhanced bioavailability, is potentially needed to 67 produce beneficial effects in humans. Piperine has been used in combination with 68 neutraceuticals such as coenzyme Q10, beta-carotene, and resveratrol to enhance their 69 bioavailability and bioefficacy (Badmaev et al. 1999; Badmaev et al. 2000; Johnson et al. 2011; 70 Wightman et al. 2014). Therefore, it seems plausible that co-supplementing resveratrol with 71 piperine could lead to enhanced bioavailability and bioefficacy of resveratrol and improve the 72 ability to produce physiological benefits in humans yet minimize the potential risks associated 73 with high doses (Mennen et al. 2005). ...
Article
Full-text available
Physical inactivity reduces, and exercise training increases, mitochondrial capacity. In rodents, exercise training effects can be augmented by large doses of resveratrol supplementation but whether this can occur in humans with a smaller dose is unclear. This study sought to determine the effects of resveratrol supplementation in combination with exercise training on skeletal muscle mitochondrial capacity. Sixteen healthy young adults were randomly assigned in a double-blind fashion to consume either placebo or 500 mg of resveratrol plus 10 mg of piperine, a bioenhancer to increase bioavailibilty and bioefficacy of resveratrol. Participants ingested the pills daily for 4 weeks and completed 3 sessions per week of submaximal endurance training of the wrist flexor muscles of the nondominant arm. The contralateral arm served as an untrained control. Skeletal muscle mitochondrial capacity was measured using near-infrared spectroscopy. Changes in mitochondrial capacity from baseline to post-testing indicated significant differences between the resveratrol+piperine-trained arm and the placebo-trained arm (p = 0.02), with the resveratrol+piperine group increasing about 40% from baseline (Δk = 0.58), while the placebo group increased about 10% from baseline (Δk = 0.13). Neither the placebo group nor the resveratrol+piperine group exhibited changes in mitochondrial capacity in the untrained arm. In conclusion, low-intensity exercise training can increase forearm skeletal muscle mitochondrial capacity when combined with resveratrol and piperine supplementation.
... represented the practical possibility of increment in the bioavailability of various nutrients. Patients observed with low levels of coenzyme Q10 in plasma and elderly people having poor gastrointestinal absorption were seen to have improved conditions when treated with piperine which actually acted as a potent bioenhancer for them (Badmaev, Majeed, & Prakash, 2000). ...
Chapter
Black pepper is known for its pungent constituent piperine. It has wide culinary uses and also possess certain preservative and medicinal properties. Piperine, beyond pungency, has been found to possess bio-transformative effects that can detoxify pathogen, prevent oxidation, and improve the bioavailability and absorption of various drugs. Piperine also shows immunomodulatory, antiasthmatic, anticarcinogenic, antiulcer, antiamoebic, antioxidant, antiinflammatory, and antiulcer properties. On the other hand, curcumin, the curcuminoid of turmeric, mainly found in rhizomes of Curcuma spp., helped to prevent skin cancers, duodenum, forestomach, and colon cancers in mice. In India and many other regions of the world, piperine and curcumin have been part of the folk formulations used for treating various ailments for centuries. In this chapter, the recent developments regarding chemistry, extraction processes, pharmacological, and biological activities of both piperine and curcumin have been discussed.
... Earlier published reports suggest that piperine can reduce high-fat diet induced oxidative stress [22]. Piperine has been shown to increase plasma levels of orally supplemented coenzyme Q 10 [23]. Moreover, piperine has also been demonstrated to inhibit cancer stem cell self-renewal properties [24]. ...
Article
Increased bone fracture is one of the health risk factors in patients with bone loss related disorders such as osteoporosis and breast cancer metastasis to bone. Over activity of osteoclasts leads to uncoupling of bone remodeling favoring bone loss over bone formation. Receptor activator of nuclear factor-κβ ligand (RANKL) triggers the differentiation pathway leading to multinucleated osteoclast formation. Modulation of RANKL or its downstream signaling pathways involved in osteoclast formation is of significant interest in the development of anti-resorptive agents. In this study, the effects of piperine, an alkaloid present in Piper nigrum L. on osteoclast formation was investigated. Piperine inhibited tartrate-resistant acid phosphatase-positive multinucleated osteoclast formation in murine RAW264.7 macrophages and human CD14+ monocytes induced by RANKL and breast cancer cells. Piperine attenuated the p38-mitogen activated protein kinase pathway activation, while the extracellular-signal-regulated kinase, c-Jun N-terminal kinase, or NF-κβ pathways downstream of RANKL remained unaffected. Concomitantly, expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcription factors involved in osteoclastogenesis were remarkably inhibited by piperine. Furthermore, piperine disrupted the actin ring structure and bone resorption, a characteristic hallmark of osteoclasts. Collectively, these results suggested that piperine inhibited osteoclast differentiation by suppressing the p38/NFATc1/c-Fos signaling axis. © 2015 BioFactors, 2015.
... Mushtaq, 978-0-12-822923-1 low levels of coenzyme Q10 in plasma and elderly people having poor gastrointestinal absorption were seen to have improved conditions when treated with piperine which actually acted as a potent bioenhancer for them (Badmaev, Majeed, & Prakash, 2000). ...
Chapter
A Centum of Valuable Plant Bioactives
... 18 This drug have anti-inflammatory activity, analgesic, and support the metabolic process of digestion. 19,20 Piperine was found to be non-specific inhibitors on the metabolism of drugs and xenobiotics. Piperine inhibits the cytochrome P450 as well as hepatic UDP-glucuronyltransferase and arylhydrocarbon hydroxylase and other enzymes contained in the drug and xenobiotic. ...
Article
Full-text available
Background: Since the last few decades, oral cancer as pathology has become an attention in medicine and dentistry. The majority cases of oral cancer are affecting people with smoking habit and alcohol consumption. Many herbs contain substances which can stop cancer cells proliferation, such as Piper retrofractum/Retrofracti fructus, an herb plant from Piperaceae family which contains piperin and piplartin. Purpose: The purpose of this study was to examine the mechanism of piperin and pilplartin as natural oral anticancer drug. Reviews: Piperin and piplartin has function as antioxidant that can protect body cell from damage caused by free radicals. Piperin works synergistically with another bioactive substance like capsaicin and curcumin. Piperin increase the number of serum and life time of serum from a few nutrition substance like co-enzyme Q10 and beta-carotene. Beta-carotene can catch reactive O2 and peroxil radicals. The activity of anticancer piplartin related with obstruction of proliferation cell rate, observe form Ki67 reduction as antigen in nucleus that associated with G1, S, G2, and M phase in cell cycle. Comparing with piplartin, piperin is more potential to inhibit proliferation rate of Ki67, but piplartin’s antiproliferation mechanism will increase if supported by piperin. Conclusion: Piperin and piplartin contained in Javanese chili are potential for natural oral anticancer, by directly or indirectly suppress tumor cell development by increasing the number of immunity cells (immunomodulator), and by inhibiting cell proliferation with reduction of Ki67, nucleus antigen that associated with G1,S,G2, dan M phase of cell cycle.Latar belakang: Sejak beberapa dekade terakhir, patologi kanker rongga mulut telah banyak menjadi perhatian di bidang kedokteran dan kedokteran gigi. Risiko paling tinggi ditemukan pada penderita perokok dan peminum alkohol. Banyak tanaman herbal yang memiliki kandungan untuk menghambat pertumbuhan sel kanker atau antiproliferasi sel, seperti tanaman herbal yang berasal dari suku Piperaceae, salah satunya adalah cabe jawa (Piper retrofractum) yang mengandung piperin dan piplartin. Tujuan: artikel ini bertujuan untuk mengetahui mekanisme kerja piperin dan pilplartin sebagai antikanker alami rongga mulut. Tinjauan pustaka: Piperin dan piplartin berfungsi sebagai antioksidan yang dapat melindungi sel tubuh dari kerusakan akibat radikal bebas. Piperin bekerja secara sinergis dengan zat-zat bioaktif lainnya seperti capsaicin dan curcumin. Piperin meningkatkan jumlah serum dan umur serum dari beberapa substansi nutrisi seperti koenzim Q10 dan betakaroten. Betakaroten mampu menangkap oksigen reaktif dan radikal peroksil. Aktivitas antitumor piplartin berhubungan dengan penghambatan laju proliferasi sel, ditinjau dari reduksi Ki67 yaitu antigen pada inti sel yang berasosiasi dengan G1, S, G2, dan M pada siklus sintesa sel. Dalam mekanisme kerjanya piplartin akan lebih meningkat aktivitas antiproliferasinya jika disinergiskan dengan piperin. Kesimpulan: Piperin dan piplartin yang terkandung dalam cabe jawa berpotensi sebagai antikanker rongga mulut alami, dengan menekan perkembangan sel tumor baik secara langsung maupun tidak langsung melalui peningkatan sel imun (immunomodulator), dengan penghambatan laju proliferasi sel, ditinjau dari reduksi Ki67, yaitu antigen pada inti sel yang berasosiasi dengan G1, S, G2, dan M pada siklus sintesis sel.
... PP can promote the absorption of -carotene (vitamin A) and vitamin B6 by interfering the substance removal process from cells by the "pump" protein p-glycoprotein. PP has also been reported to facilitate the absorption of the active components of healthy food products such as turmeric and coenzyme Q10 [22]. The application to the food field is expected for the pharmaceutical research complexation technique of medical supplies. ...
Article
Full-text available
Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and β -cyclodextrin ( β CD) (molar ratio of PP/ β CD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and β CD were observed. Based on Job’s plot, the PP/ β CD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH 2 ), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure β CD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and β CD cavity was detected by 1 H- 1 H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy.
... [17] Some of the scientifically documented drugs, which are affected by "piperine" co-administration are cited in Table 1. [7,[18][19][20][21][22][23][24][25][26] ...
... BioPerine ® with thermonutrient activity and bioavailability enhancement properties is a natural product. A thermonutrient is a nutrient with properties stimulated the bioenergetic processes in the gastrointestinal epithelium [47]. It has been observed that the administration of a preparation of beta-carotene (15 mg) plus Bioperine ® (5mg) increases the levels of beta-carotene by approximately 2 times in humans. ...
Article
Full-text available
Black pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study aimed to describe the impact of the joint administration of iron (Fe) plus black pepper in physically active healthy individuals. Fe is a micronutrient that aids athletic performance by influencing the physiological functions involved in endurance sports by improving the transport, storage, and utilization of oxygen. Consequently, athletes have risk factors for Fe depletion, Fe deficiency, and eventually, anemia, mainly from mechanical hemolysis, gastrointestinal disturbances, and loss of Fe through excessive sweating. Declines in Fe stores have been reported to negatively alter physical capacities such as aerobic capacity, strength, and skeletal muscle recovery in elite athletes. Thus, there is a need to maintain Fe storage, even if Fe intake meets the recommended daily allowance (RDA), and Fe supplementation may be justified in physically active individuals, in states of Fe deficiency, with or without anemia. Females, in particular, should monitor their Fe hematological profile. The recommended oral Fe supplements are ferrous or ferric salts, sulfate, fumarate, and gluconate. These preparations constitute the first line of treatment; however, the high doses administered have gastrointestinal side effects that reduce tolerance and adherence to treatment. Thus, a strategy to counteract these adverse effects is to improve the bioavailability of Fe. Therefore, piperine may benefit the absorption of Fe through its bioavailability enhancement properties. Three research studies of Fe associated with black pepper have reported improvements in parameters related to the metabolism of Fe, without adverse effects. Although more research is needed, this could represent an advance in oral Fe supplementation for physically active individuals.
... The inter subject changes were diminished by careful selection of experimental volunteers to healthy men with coenzyme Q10 fasting values 0.30 and 0.60 mg/L, respectively. The resultant data of single and the 14 day trial showed lesser rise in coenzyme Q10 concentrations of plasma in control as compared to individuals getting coenzyme Q10 with piperine as a supplement (Badmaev et al., 2000). ...
Article
Contemporary nutrition regime has focused the attention of the researchers on phytochemicals enriched spices to mitigate various oncological threats. Numerous chemopreventive strategies against malignancy have been developed considering the anticancer perspectives of allied nutraceutical constituents. Current evidences have proven an inverse association of spices with that of oncological incidences. The high antioxidant activity of spices derived bioactives triggers the free radicals scavenging ability at cellular level thereby alleviating various metabolic syndromes. Promising compounds including curcumin and curcuminoids (turmeric), limonene (cardamom), allicin, allyl isothiocyanate (garlic), cinnamic aldehyde, 2-hydroxycinnamaldehyde and eugenol (cinnamon), gingerol, zingiberone, zingiberene (ginger), dipropyle disulfides and quercetin (onion), piperidine piperine, limonene, α- and β-pinene (black pepper), crocetin, crocin and safranal (saffron) have been identified as chemopreventing agents against various malignancies. Chemopreventive properties of spices are mediated by functional bioactive ingredients that arrest the activity of cytochrome P450 and isozymes CYP 1A1, cyclooxygenase-2, reducing activator of transcription-3 (STAT-3) and signal transducer. They are closely associated with tumorigenesis activated by interleukin-6 (IL-6) receptors and epidermal growth factor (EGF) relate to an array of tumors. The bioactive constituents altering the expression of protein involved in cell cycle, activating caspases killer and suppressing Kappa-B activation. Alongside, they also restrain causative agents of cell structure damage as in lipid and protein membrane system and DNA that shifting healthy body towards cancerous state. Spices phytochemicals have established as carcinogenesis blockers by modulating cell proliferation pathways transformation, inflammation, metastasis etc. Furthermore, spices as functional ingredients may act as immune boosters and diminish inflammatory disorders. The current review is inevitably an affirmative approach in the development of novel guidelines against cancer by using dietary species to maintain good health.
... CARDIOL ® Forte is dietary supplement containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), hydroxytyrosol polyphenol of olive oil, coenzyme Q10, folic acid, B 12 and E vitamins, piperine, and monacolin K (10 mg) from red yeast rice (RYR), whose components have demonstrated to have lipid-lowering action and/or endothelial protective action [9][10][11][12][13][14]. ...
Article
Introduction: There is growing interest in lipid-lowering nutraceuticals; however, there are a relative scarcity of data on combined compounds. This study was aimed to assess the efficacy and tolerability of a combined nutraceutical (CARDIOL® Forte - CF) containing polyunsaturated fatty acids, hydroxytyrosol, Coenzyme Q10, folic acid, B12 and E vitamins, piperine, and red yeast rice in patients with mild-to-moderate hypercholesterolaemia. Material and methods: In this single-centre, double-blinded, placebo-controlled study enrolled subjects who were randomised to receive the tested combined nutraceutical for 16 weeks (CF group) or placebo (control group), in association with a low-fat diet. After 8 weeks of treatment, all patients underwent a 15-day washout period; then, a further 8 weeks of treatment was planned. Results: Of 80 enrolled subjects, 37 completed the study in the CF group and 38 in the control group. After 8 weeks of treatment, low-density lipoprotein cholesterol levels were reduced by 17% in the CF group and by 6.4% in the control group, compared to baseline (p = 0.0001); these changes were improved at the end of study. Total cholesterol and triglyceride levels significantly decreased during treatment; high-density lipoprotein cholesterol did not change. In the CF group, flow-mediated dilation increased by 18.8% after 8 weeks and by 39.3% at the end of treatment. No adverse events or musculoskeletal disorders were reported in either group. Conclusions: The tested combined nutraceutical, in association with a controlled diet, can reduce cholesterol levels and improve endothelial function, thus reducing the cardiovascular risk in patients with mild-to-moderate hypercholesterolaemia.
... Inhibition of these enzymes results in increasing the availability of numerous compounds absorbed in GI tract [92, 96 -98]. Piperine from Black pepper also increases the plasma levels of co-enzymes Q10 [99] and serum response of beta carotenes followed by oral supplementation [100] and thus proves to be thermogenic by nature. Table 2. Bioenhancer effect of piperine with some medicines. ...
Article
Full-text available
Piper nigrum L. is examined as the king of species worldwide by virtue of its principle piperine. In Ayurveda, since from the ancient times, it is known as “Yogvahi”. It is one of the important alkaloids of Pepper fruits (Family Piperaceae) and has been found to have numerous medicinal properties such as antioxidant, antiplatelet, anti-inflammatory, antihypertensive, hepatoprotective, antithyroid, antitumor, antiasthmatic activity and also have significant role as fertility enhancer. The present review discusses the biosynthetic pathway, extraction process, chemistry and various analytical methods of piperine. It also describes the structural modification of piperine and its various effects on biological system. The utility of piperine as a bioenhancer for certain antibacterial- antibiotics and a potent inhibitor of drug metabolism are also discussed. Thus, review provides knowledgeable erudition on the piperine which paves way for further work. Piper nigrum L. is examined as the king of species worldwide by virtue of its principle piperine. In Ayurveda, since from the ancient times, it is known as “Yogvahi”. It is one of the important alkaloids of Pepper fruits (Family Piperaceae) and has been found to have numerous medicinal properties such as antioxidant, antiplatelet, anti-inflammatory, antihypertensive, hepatoprotective, antithyroid, antitumor, antiasthmatic activity and also have significant role as fertility enhancer. The present review discusses the biosynthetic pathway, extraction process, chemistry and various analytical methods of piperine. It also describes the structural modification of piperine and its various effects on biological system. The utility of piperine as a bioenhancer for certain antibacterial- antibiotics and a potent inhibitor of drug metabolism are also discussed. Thus, review provides knowledgeable erudition on the piperine which paves way for further work.
Article
Metformin hydrochloride is a biguanide, which is used as an oral hypoglycemic agent. It is prescribed as a antidiabetic agent specifically for type-2 diabetes mellitus. Metformin hydrocloride has poor absorption when given orally is 50-60%.The present study is to enhance the oral absorption of metformin hydrochloride by using herbal absorption enhancer i.e. piperine. To enhance the absorption of poorly absorbable drugs from intestine. The invitro Non-everted sac modification method is selected for the absorption studies. The absorption studies are conducted for poorly absorbable drug Metformine HCl in the presence of herbal like black pepper (piperine, Showed an increase in intestinal brush border membrance (BBM) fluidity). During the absorption study, the sample from intestinal are collected for every 15minutes interval and up to 2hrs at 233nm.The absorbed drug was analysed by using UV-spectrophotometer. By results of all experimental, it is concluded that the piperine enhancing the absorption activity of Metformine Hcl.
Article
Pepper extracts in ethanol and acetone and the commercial pepper oil are used to determine the percentage of piperine using high pressure liquid chromatography (HPLC) analysis. The extracts were tested for their anti-bacterial and anti-fungal activities with several species of Aspergillus and bacterial isolates from the rhizosphere of pepper. The acetone extract with 94% piperine showed better antimicrobial property. The bacterial and fungal isolates tested showed varying degrees of sensitivity towards pepper oil, pepper alcoholic extract and acetone extract of pepper. A.niger (78.8 mm) was completely inhibited with acetone extract while Bacillus subtilis (46.1 mm), Bacillus sp. (44.7 mm) and other bacterial species were significantly inhibited by the pepper extracts. MIC of pepper extracts and pepper oil resulted in a higher value for acetone extract indicating its efficiency as an antimicrobial agent. Antioxidant activity of various pepper extracts showed variable results with three different methods- 2, 2-Diphenly 1-picryl hydrazyl (DPPH), superoxide dismutase scavenging and scavenging by nitric oxide. Pepper ethanolic extract showed the greatest activity with DPPH method.
Book
The Chemistry inside Spices & Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included. Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin. Audience: This book is an ideal resource for scholars (in life sciences, phytomedicine and natural product chemistry) and general readers who want to understand the importance of herbs, spices and traditional medicine in pharmaceutical and clinical research.
Article
Context: Piperine alkaloid, an important constituent of black pepper exhibits numerous therapeutic properties whereas its usage as a drug is limited due to its poor solubility in aqueous medium, which leads to poor bioavailability. Objective: Herein a new method has been developed to improve the solubility of this drug based on the development of solid dispersions with improved dissolution rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG) and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of piperine and carriers were also prepared for comparison. Methods: The physicochemical properties of the prepared solid dispersions were examined using SEM, TEM, DSC, XRD and FT-IR. In-vitro dissolution profile of the solid dispersions was recorded and compared with that of the pure piperine and physical mixtures. The effect of these carriers on the aqueous solubility of piperine has been investigated. Results: The solid dispersions of piperine with Sor, PEG and PVP exhibited superior performance for the dissolution of piperine with a drug release of 70%, 76% and 89% respectively after 2 h compared to physical mixtures and pure piperine, which could be due to its transformation from crystalline to amorphous form as well as the attachment of hydrophilic carriers to the surface of poorly water-soluble piperine. Conclusion: Results suggest that the piperine solid dispersions prepared with improved in-vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement.
Article
Radiation damage can occur in nuclear power plant workers when physical protections fail, which results in nuclear leakage through the protective layers. Alternatively, workers may be unable to use physical protection in time (in the case of a sudden nuclear weapons attack). In addition, patients who receive local radiotherapy and are not allowed to adopt local physical protection may experience radiation damage. Thus, protection against chemical radiation has become indispensable. In view of the side effects caused by synthetic radioprotective agents (such as amisfostine), searching for radioprotective agents from plant sources is an alternative strategy. Radiation damage can cause multiple signalling pathway disturbances, leading to multiple organ injuries. Changes in these signalling pathways can lead to apoptosis, necrosis, and autophagy, as well as organ fibrosis, atrophy, and inflammation. Through literature searches, we determined that most targets for treating radiation injury are mechanistically opposite those of anti-tumour agents. This is likely attributable to the idea that anti-tumour agents promote cell necrosis or apoptosis, whereas the goal of anti-radiation agents is to promote cell survival or autophagy. This observation has important theoretical and practical significance when searching and developing new radioprotective agents derived from plant extracts. Further, it has important guiding value for meeting military needs and serving the public.
Article
In the present study, the fabrication and characterization of novel core-shell-type surface-engineered nanoparticles were reported for co-encapsulation of coenzyme Q10 and piperine, which were natural nutraceuticals with synergistic biological activities. Initially, nutraceutical-loaded zein nanoparticles were formed by antisolvent precipitation method. Then, κ-carrageenan was adsorbed to the surface of zein nanoparticles using electrostatic deposition. Finally, the κ-carrageenan layer was induced into a hydrogel shell by using K⁺ as a cross-linking agent. At low K⁺ levels (0–4 mmol/L), the relatively small spherical anionic nanoparticles were formed and were stable. However, at high K⁺ levels (4–10 mmol/L), the nanoparticles formed were relatively large and tended to aggregate. A photodegradation result showed that the half-lives of coenzyme Q10 and piperine were increased by 3.0- and 1.8-fold, respectively, when encapsulated in the biopolymer nanoparticles compared to the free forms. Moreover, their retention rates were increased by 151% and 200% during thermal treatment, and 111% and 131% during a four-week storage, respectively. Besides, the release of the nutraceuticals from the biopolymer nanoparticles in a simulated gastrointestinal tract could be retarded by increasing the degree of interfacial cross-linking. In summary, the core-shell nanoparticles developed here are an effective approach for the co-delivery of synergistic nutraceuticals.
Article
Full-text available
Black pepper is an autoicous and decorous vine cultivated and harvested in tropical regions of Srilanka and India. Black pepper is one of the most commonly consumed spice, and its pungency is due to the presence of an alkaloid known as piperine, volatile chemical constituents, and essential oils. Piperine is found in black pepper, white pepper and long pepper belonging to the family Piperaceae. Piperine represents diverse biological activities, such as anti-inflammatory, anticancer, antiviral, anti-larvicidal, pesticide, anti-Alzheimer’s, antidepressant and most importantly piperine is known as the bioavailability enhancer. The current review article aims to explore the extraction of piperine from different species of pepper, its total synthesis, and the pharmacokinetic study and various biological activities of piperine. Further, different combinations of piperine with available marketed drugs to improve the bioavailability have also been included. Different studies on piperine suggest that piperine acts as an excellent bio-enhancer to improve the bioavailability of drugs with poor ADMET properties. Some study also indicates that piperine shows synergistic effects when taken in combination with various classes of drugs.
Article
The aim of this present work was to fabricating a novel multilayer structural microparticle based on zein, pectin and chitosan for co-encapsulating of nutraceuticals. Coenzyme Q10 and piperine has many physiological activities and synergistic effects, but it was challenging to co-embed them in the traditional delivery systems due to their different molecular polarities. In this study, Coenzyme Q10 was embedded into the hydrophobic zein core because it is a strongly hydrophobic molecule, whereas piperine was trapped between the polysaccharide layers (negative pectin and positive chitosan) because it is only a weakly hydrophobic molecule. The effects of low, medium, and high levels of chitosan layer thickness on the formation of the multilayer structural microparticles were studied, and the low level of chitosan layer thickness was the most suitable to form the relatively small (922 nm) and positively charged (+49.2 mV) microparticles. The entrapment efficiency of the multilayer structural microparticles was 88.7% for coenzyme Q10, and 77.2% for piperine, respectively. The microparticles protected coenzyme Q10 and piperine from chemical degradation during exposure to light, heat, and long-term storage, as well as modulated their release in simulated gastrointestinal digestion. This work would contribute to the development of more efficacious co-delivery systems for synergistic nutraceuticals with different polarities.
Article
As a BCS Ⅳ drug, ursolic acid (UA) has low oral bioavailability mainly because of its poor aqueous solubility/dissolution, poor permeability, and metabolism by cytochrome P450 (CYP) isozymes, such as CYP3A4. Most UA preparations demonstrated a much higher dissolution than that of its crystalline form, yet a low drug concentration in plasma due to their less consideration or evaluation for the permeability and metabolism issues. In the current study, a supramolecular co-amorphous system of UA with piperine (PIP) was prepared, and characterized by powder X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. In comparison to crystalline UA and UA in physical mixture, such co-amorphous system enhanced solubility (5.3-7 folds in the physiological solution) and dissolution (7-8 folds in the physiological solution within two hours) of UA, and exhibited excellent physical stability under 90-day storage conditions. More importantly, the pharmacokinetic study of co-amorphous UA in rats exhibited 5.8-fold and 2.47-fold improvement in AUC0-∞ value, respectively, compared with its free and mixed crystalline counterparts. In order to further explore the mechanism of such improvement, the molecular interactions of co-amorphous system in the solid state were investigated. Fourier transform infrared spectroscopy, solid-state 13C nuclear magnetic resonance spectroscopy and density functional theory modeling suggested that intermolecular hydrogen bonds with strong interactions newly formed between UA and PIP after co-amorphization. The in vitro permeability studies across Caco-2 cell monolayer and metabolism studies by rat hepatic microsomes indicated that free PIP significantly increased the permeability of UA and inhibited the enzymatic metabolism of UA by CYP3A4. However, PIP in the co-amorphous combination exhibited a much lower level in the bio-enhancing than its free form arising from the synchronized dissolution characteristic of the preparation (only 60% of PIP released in comparison to its free counterpart in 2 h). The in-situ loop study in rats proposed that the acid-sensitive dissolution in the stomach of the co-amorphous preparation helped to improve the effective free drug concentration, thereby facilitating PIP to play its role in bio-enhancing. The current study offers an exploratory strategy to overcome poor solubility/dissolution, poor permeability and metabolism by cytochrome P450 isozymes of the BCS Ⅳ drug to improve its oral bioavailability.
Article
Long‐recognized physiological actions of black pepper Piper nigrum and turmeric Curcuma longa plants or their active ingredients (piperine [Pip] and curcumin [Curc], respectively) have been tested in nutritional and clinical experiments. Available data suggest that both dietary additives influence food acceptance, metabolism, and digestive physiology and increase the bioavailability of several drugs and nutrients. Therefore, the main goal of this study was to test how Common Carp Cyprinus carpio respond to diets supplemented with Pip, Curc, and black pepper extract (BP) in terms of food intake, growth, whole‐body composition, and muscle free amino acid (FAA) levels. We used the following dietary treatments: a reference diet based on casein and gelatin (CG), a diet in which a fraction of CG protein (20%) was replaced with an FAA mixture (Met0.4 [methionine 0.4%]), and three other diets identical to Met0.4 but supplemented with 0.02% Pip, Curc, or BP. We found that addition of spices and their active ingredients impacted fish growth (BP depressed growth by 30%); however, these dietary additives did not show any significant effect on food intake across the treatments. Dietary Pip increased total lipids in the whole body. The total indispensable FAA level was higher in the Curc group compared to the CG group only. The total dispensable FAA level in the BP group was higher than those in the CG and Met0.4 groups but was not different than those in the Pip and Curc groups. We conclude that further study is warranted with different levels of spices in fish diets. A summary of the current state of knowledge on the effect of Pip on nutrient flux and nutrient utilization, as well as possible regulatory mechanism(s) involved in the action of spices in fish, with a focus on Pip, is also provided.
Article
Background Psoriasis is an autoimmune disorder that affects the skin and is characterized by irritation, red, flaky patches over different parts of the body. The present study intended to design and evaluate Acitretin (ACT) loaded nanostructured lipid carriers (NLCs) to manage psoriasis through topical application. ACT is an analog of vitamin A used to control psoriasis via the oral route. The prime demerit associated with oral route delivery of a drug is the teratogenic effect associated with the active molecule and side effects like dry mouth, runny nose, hair loss, taste changes, chapped lips, etc. These are the major contributing factors to reduced patient compliance. Objective The objective of the present research work was to develop a topical formulation of ACT. Developing topical formulation for the same can result in enhanced patient compliance and can be worth compared to the marketed oral formulation of the drug. Methods ACT loaded NLCs were prepared by hot homogenization method using oleic acid as a liquid lipid and stearic acid as a solid lipid in a 7:3 ratio along with the combination of a non-ionic surfactant (Tween 80) and an anionic surfactant ( sodium lauryl sulphate). Results In several optimization experiments formulation, F3 was found to be most appropriate for formulating gel. Morphological information obtained from SEM reinforced the formation of particles with nearly spherical morphology. The optimized formulation had a mean diameter of 363nm, as founded by Zetasizer. XRD studies affirmed that the formulation exhibits amorphous nature, which is an essential character of NLC. An optimized formulation was further incorporated in the gel by using Carbopol 940P as a gelling agent. In vitro release studies indicated 96.85 ± 2% release in 8 hours with Korsmeyer- Peppas model release kinetics. The observed n value1.391 for drug release for F3G2 bespeak Super case II transport maybe result from sorption of the drug from the surface of NLC controlled by stress-induced relaxation boundary of the swollen shell. Conclusion In vitro characterization of ACT (Acitretin) loaded NLC supports the objective that NLC can serve as a potential carrier for topical delivery of ACT and can also reduce oral toxicity associated with drug after stringent evaluation in the near future.
Article
Ischemic stroke (IS) is a rapidly increasing global burden and is associated with severe neurological decline and mortality. There is urgent requirement of the efforts, aimed to identify therapeutic strategies that are effective in clinic to promote significant recovery from IS. Studies have shown that mitochondria mediated neuroprotection can be a competent target against ischemic damage. Therefore, we examined whether mitochondrial impairment is regulated by Piperine (PIP), an alkaloid of Piper Longum, which has neuroprotective activity against ischemic brain injury. In this study, transient middle cerebral artery occlusion (tMCAO) surgery was performed on male Wistar rats for 90 min followed by 22.5 h of reperfusion for mimicking the IS condition. This study consisted of three groups: sham, tMCAO and tMCAO + PIP (10 mg/kg b.wt., p.o/day for 15 days), and studied for behavioral tests, infarct volume, brain pathological changes, mitochondrial dysfunction, inflammation alongwith cell survival status. PIP pre-treatment showed reduction in neurological alterations and infarct volume. In addition, PIP pre-treatment suppressed the mitochondrial dysfunction and might have anti-apoptotic potential by preventing Cytochrome c (Cyt c) release from mitochondria to cytoplasm and caspase 3 activation. It also regulates pro-apoptotic, Bax and anti-apoptotic, Bcl-2 proteins accompanied by glial fibrillary acidic protein (GFAP) positive cells in cortex region. Quantitative Reverse transcription-polymerase chain reaction (qRT-PCR) results also showed that PIP reduced the expression of pro-inflammatory protein, interleukin-1 β (IL-1β) and enhanced cell survival by restoring the activity of brain derived neurotrophic factor (BDNF) and its transcription protein, cAMP response element binding protein (CREB). Taken together, PIP reduced the mitochondrial dysfunction, neurological impairment, and enhanced neuronal survival. In conclusion, our findings reinforce PIP as an effective neuroprotective agent and provide important evidence about its role as a potential target to serve as a promising therapy for treatment of IS.
Article
This study aimed to evaluate the role of spices/spice active principles on physical, biochemical, and molecular targets of bioaccessibility/bioavailability. Carotenoids‐rich micellar fraction obtained through simulated digestion of green leafy vegetables (GLV) with individual or two/three combinations were correlated to their influence on bioaccessibility, cellular uptake, and basolateral secretion of carotenoids in Caco‐2 cells. Results suggest that carotenoids' bioaccessibility depends on micelles physicochemical properties, which is affected due to the presence of co‐treated dietary spices and their composition. Increased bioaccessibility of β‐carotene (BC) and lutein (LUT) is found in GLV (spinach) digested with turmeric (TM) than red pepper (RP) and black pepper (BP). In contrast, enhanced cellular uptake and secretion of BC and LUT‐rich triglyceride‐rich lipoprotein is observed in the presence of RP and BP compared to the control group. In contrast, TM inhibited absorption, while retinol levels significantly reduced in the presence of TM and RP than BP. Control cells have indicated higher cleavage of β‐carotene to retinol than the spice‐treated group. Besides, spice active principles modulate facilitated transport of carotenoids by scavenger receptor class B type 1 (SR‐B1) protein. The effect of spices on carotenoids’ bioavailability is validated with active spice principles. Overall, carotenoids’ bioavailability (cellular uptake and basolateral secretion) was found in the following order of treatments; piperine > capsaicin > piperine + capsaicin > curcumin + capsaicin + piperine > control > turmeric. These findings suggested that the interaction of specific dietary factors, including spice ingredients at the enterocyte level, could provide greater insight into carotenoid absorption. Spices/spice active principles play a role in the digestion process by stimulating digestive enzymes and bile acids secretion. Since carotenoids are lipid soluble and have low bioavailability, spice ingredients' influence on intestinal absorption of carotenoids is considered crucial. Hence, understanding the interaction of co‐consumed spices on the absorption process of carotenoids may help to develop functional foods/formulation of nutraceuticals to improve their health benefits.
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Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes. Although the nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery. Bioenhancers (drug absorption enhancers of natural origin) have been identified that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism. The aim of this paper is to provide an overview of natural bioenhancers and their main mechanisms of action for the nasal, buccal, pulmonary and oral routes of drug administration. Poorly bioavailable drugs such as large, hydrophilic therapeutics are often administered by injections. Bioenhancers may potentially be used to benefit patients by making systemic delivery of these poorly bioavailable drugs possible via alternative routes of administration (i.e., oral, nasal, buccal or pulmonary routes of administration) and may also reduce dosages of small molecular drugs and thereby reduce treatment costs.
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A new composition and method for the improvement of gastrointestinal absorption and systemic utilization of nutrients and nutritional supplements, wherein the composition comprises an extract from the fruit of Piper containing a minimum of 98% of pure alkaloid piperine. The method comprises oral, topical, or parenteral administration of the composition of the invention. A new process for the extraction and purification of piperine is also disclosed.
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As the oxidation of low density lipoprotein (LDL) lipids may be a key event in atherogenesis, there is interest in antioxidants as potential anti-atherogenic compounds. Here we report that alpha-tocopheryl hydroquinone (alpha-TQH2) strongly inhibited or completely prevented the (per)oxidation of ubiquinol-10 (CoQ10H2), alpha-tocopherol (alpha-TOH), and both surface and core lipids in LDL exposed to either aqueous or lipophilic peroxyl radicals, Cu2+, soybean lipoxygenase, or the transition metal-containing Ham's F-10 medium in the absence or presence of human monocyte-derived macrophages. The antioxidant activity of alpha-TQH2 was superior to that of several other lipophilic hydroquinones, including endogenous CoQ10H2, which is regarded as LDL's first line of antioxidant defence. At least three independent activities contributed to the antioxidant action of alpha-TQH2. First, alpha-TQH2 readily associated with LDL and instantaneously reduced the lipoprotein's ubiquinone-10 to CoQ10H2, thereby maintaining this antioxidant in its active form. Second, alpha-TQH2 directly intercepted aqueous peroxyl radicals, as indicated by the increased rate of its consumption with increasing rates of radical production, independent of LDL's content of CoQ10H2 and alpha-TOH. Third, alpha-TQH2 rapidly quenched alpha-tocopheroxyl radical in oxidizing LDL, as demonstrated directly by electron paramagnetic resonance spectroscopy. Similar antioxidant activities were also seen when alpha-TQH2 was added to high-density lipoprotein or the protein-free Intralipid, indicating that the potent antioxidant activity of alpha-TQH2 was neither lipoprotein specific nor dependent on proteins. These results suggest that alpha-TQH2 is a candidate for a therapeutic lipid-soluble antioxidant. As alpha-tocopherylquinone is formed in vivo at sites of oxidative stress, including human atherosclerotic plaque, and biological systems exist that reduce the quinone to the hydroquinone, our results also suggest that alpha-TQH2 could be a previously unrecognized natural antioxidant.
Article
The effectiveness of an extract from the fruit of black pepper, consisting of a minimum of 98.0% pure alkaloid piperine, was evaluated for its ability to improve serum response of beta-carotene during oral supplementation using a double-blind, crossover study design. Subjects were randomly selected to ingest a daily beta-carotene dose (15 mg) either with 5 mg of piperine or placebo during each of two 14-day supplementation periods. Inter-subject variability in pre-supplementation serum beta-carotene levels was minimized by limiting the selection of volunteers to healthy, adult males with fasting serum beta-carotene values <20 μg/dL. The results indicate that significantly greater increases (P<0.0001) in serum beta-carotene occurred during supplementation with beta-carotene plus piperine (49.8±9.6μg/dL vs. 30.9±5.4μg/dL) compared to beta-carotene plus placebo. Supplementation with beta-carotene plus piperine for 14-days produced a 60% greater increase in area under the serum beta-carotene curve (AUC) than was observed during supplementation with beta-carotene plus placebo. We suggest that the serum response during oral beta-carotene supplementation is improved through the non-specific, thermogenic property(s) of piperine, described in this paper as thermonutrient in action.
Pepper is the most important of the spices, with a long history. This article critically reviews our knowledge of the chemistry, processing, and quality evaluation of the product, with emphasis on the constituents contributing to the sensory properties of the spice for which it is valued in food. Other areas briefly summarized include its history, horticultural aspects, production and trade data, and physiological effects. Allied spices and aromatic members of the same family are also considered briefly.
Article
The effect of piperine (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidin e), (from Piper nigrum) on the absorptive function of the intestine was studied. In vitro experiments showed that piperine (25-100 microM) significantly stimulated gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2.) activity, enhanced the uptake of radiolabelled L-leucine, L-isoleucine and L-valine, and increased lipid peroxidation in freshly isolated epithelial cells of rat jejunum. The kinetic behaviour of gamma-GT towards substrate and acceptor altered in the presence of piperine. In the presence of benzyl alcohol, an enhanced gamma-GT activity due to piperine was maintained. These results suggested that piperine may interact with the lipid environment to produce effects which lead to increased permeability of the intestinal cells.
Article
Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested.
Article
Twenty-three randomly selected plasma samples from apparently healthy, middle aged men were analysed for coenzyme Q10 (CoQ10), alpha-tocopherol (AT) and free cholesterol (FC) in: 1) whole plasma, 2) the HDL lipoprotein fraction after LDL precipitation (VLDL + LDL). CoQ10, AT and FC in plasma averaged 0.69 +/- .11, 6.74 +/- 1.78 micrograms x ml-1 and 0.59 +/- .11 mg x ml-1 and in HDL 0.17, 3.24 micrograms x ml-1 and 0.17 mg x ml-1 or 29, 48 and 29% of plasma values. Amounts of CoQ10 and AT were correlated to that of FC in all pools. The amount of HDL-CoQ10 but not of HDL-AT fell, with the HDL-FC expressed as the fraction of plasma FC. In all pools, N-AT versus AT initially increased and then levelled off, indicating saturation like conditions in contrast to CoQ10. Thus, CoQ10 and AT are differently allocated in HDL and LDL. This might have a bearing both on the suggested lipoprotein protection against peroxidation by these two antioxidants, but also on the distribution and allocation in different organs of CoQ10 and AT by HDL and LDL transportation.
Article
The effect of piperine on the bioavailability and pharmacokinetics of propranolol and theophylline has been examined in a crossover study. Six subjects in each group received a single oral dose of propranolol 40 mg or theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7 days. An earlier tmax and a higher Cmax and AUC were observed in the subjects who received piperine and propranolol. It produced a higher Cmax, longer elimination half-life and a higher AUC with theophylline. In clinical practice, the enhanced systemic availability of oral propranolol and theophylline could be exploited to achieve better therapeutic control and improved patient compliance.
Article
The in vitro effects of piperine on three bioenergetic reactions namely, oxidative phosphorylation, ATPase activity and calcium transport by isolated rat liver mitochondria have been investigated. Piperine was found to inhibit state 3 and DNP-stimulated respiration by mitochondria respiring with glutamate plus malate or succinate as substrates. The I50 values of piperine on oxidative phosphorylation in the presence of glutamate plus malate and succinate were 22 and 12 micrograms/mg mitochondrial protein respectively. With HTM preparations, the oxidation of added NADH and succinate was depressed by piperine while ascorbate plus TMPD oxidation was slightly affected. Piperine did not inhibit the mitochondrial ATPase activity induced by DNP, but by itself exerted stimulating activity on this enzyme. Piperine was also found to diminish calcium uptake and to facilitate the release of accumulated calcium by the mitochondria incubated with succinate or ATP. These results suggest that piperine inhibits mitochondrial oxidative phosphorylation at the level of respiratory chain, and the inhibitory site(s) is in the segment(s) ahead of cytochrome C. The mechanism of the piperine-induced ATPase activity is not known; but the effect of piperine on calcium transport is likely to be consequential to the effects of this compound on the mitochondrial respiratory chain and ATPase activity.
Article
We recently reported that capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the rat adrenal medulla. In this study, the effects of some pungent principles of spices on adrenal catecholamine secretion were investigated as compared with that of capsaicin. An increase in catecholamine, especially epinephrine, secretion was observed not only on capsaicin infusion but also on piperine (a pungent principle of pepper) and zingerone (ginger) infusion. Even on infusion of the same amount (650 nmol/kg, i.v.), the order of potency as to catecholamine secretion was capsaicin much greater than piperine greater than or equal to zingerone. While, sulfur-containing and volatile pungent principles, allylisothiocyanate (mustard, etc.) and diallyldisulfide (garlic, etc.), did not even cause slight catecholamine secretion. Furthermore, these adrenergic secretagogues were readily transported via the gut into the body. These results indicate that some pungent principles of dietary spices can induce a warming action via adrenal catecholamine secretion.
Article
Pharmacokinetics of phenytoin were studied in healthy subjects. In a crossover study five volunteers received either a single oral dose (300 mg) of phenytoin alone or in combination with multiple doses of piperine (20 mg × 7 days) followed by an oral dose of phenytoin. Blood samples were collected at 0.5, 1,2,3,4,8,12,24, and 48 h after drug administration and analysed for phenytoin by the enzyme multiplied immunoassay technique (EMIT). The results obtained revealed that a single daily dose of piperine for 7 days decreased the absorption halflife (P < 0.05), prolonged the elimination halflife (P < 0.01), and produced a higher area under the drug concentration curve (P < 0.05) in comparison to phenytoin alone. It is therefore concluded that piperine on multiple dose administration alters the pharmacokinetic parameters of the antiepileptic.
The pharmacokinetics of coenzyme Q10 (CoQ10) in man was studied by utilizing deuterium-labelled coenzyme Q10 (d5-CoQ10). The absence of an isotope effect in the disposition of d5-CoQ10 in man was confirmed from the plasma concentration time curves after simultaneous oral dosing of d5-CoQ10 and unlabelled CoQ10. After oral administration of 100 mg of d5-CoQ10 to 16 healthy male subjects, the mean plasma CoQ10 level attained a peak of 1.004 +/- 0.370 micrograms/ml at 6.5 +/- 1.5 h after administration, and the terminal elimination half-life was 33.19 +/- 5.32 h. In most of the subjects, plasma d5-CoQ10 showed a second peak at 24 h after dosing. This unusual plasma level curve was well described by a newly proposed compartment model based upon the assumption that absorbed CoQ10 is taken up by the liver and then transferred mainly to VLDL and redistributed from the liver to the systemic blood.
Article
Piperine, a major active component of black and long peppers, has been reported to enhance drug bioavailability. The present studies were aimed at understanding the interaction of piperine with enzymatic drug biotransforming reactions in hepatic tissue in vitro and in vivo. Piperine inhibited arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation and 3-hydroxy-benzo(a)pyrene glucuronidation in rat postmitochondrial supernatant in vitro in a dose-dependent manner. Piperine inhibition of these reactions in postmitochondrial supernatant from 3-methylcholanthrene- and phenobarbital-treated rats was similar to the controls. Inhibition by piperine of arylhydrocarbon hydroxylase (AHH) from 3-methylcholanthrene-treated rats was comparable to that observed with 7,8-benzoflavone. Piperine caused noncompetitive inhibition of hepatic microsomal AHH from the untreated and 3-methylcholanthrene-treated rats with a Ki of 30 microM which was close to the apparent Km of AHH observed in the controls. Similarly, the kinetics of inhibition of ethylmorphine-N-demethylase from control rat liver microsomes exhibited noncompetitive inhibition with an apparent Km of 0.8 mM and Ki of 35 microM. These studies demonstrated that piperine is a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH and UDP-glucuronyltransferase activities. The maximal inhibition of AHH observed within 1 hr restored to normal value in 6 hr. Pretreatment with piperine prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice at half the dose of SKF-525A. These results demonstrate that piperine is a potent inhibitor of drug metabolism.
Article
A convenient and precise method for the separation and determination of coenzyme Q (CoQ)-related compounds (CoQ homologues, plastoquinone-9, ubichromenol-9, etc.) was developed using high-performance liquid chromatography (HPLC). All compounds tested were separated using a reverse-phase column with a suitable mobile phase and detected at a wavelength of 275 nm. CoQ extracts in plasma and erythrocytes were purified by thin-layer chromatography prior to HPLC analysis, but such purification was not necessary when determining CoQ in urine and tissues. Hydroquinone forms of CoQ existing in animal tissues were oxidized to the corresponding quinone forms with potassium hexacyanoferrate(III). This HPLC method was applied satisfactorily to the determination of the contents of CoQ homologues in human and animal samples. CoQ10 was the only homologue detected in human samples, and CoQ8, CoQ9 and CoQ10 were native homologues of CoQ in rat tissues. Ubichromenol-9 and plastoquinone-9 were not detected in these samples.
Article
Experiments were conducted to evaluate the scientific basis of the use of the trikatu group of acrids (long pepper, black pepper and ginger) in the large number of prescriptions in Ayurveda. [3H] vasicine and [3H] sparteine were taken as test drugs. Piper longum (long pepper) increased the blood levels of vasicine by nearly 233%. Under the influence of piperine, the active principle of Piper species, sparteine blood levels increased more than 100%. The results suggest that these acrids have the capacity to increase the bioavailability of certain drugs. It appears that the trikatu group of drugs increase bioavailability either by promoting rapid absorption from the gastrointestinal tract, or by protecting the drug from being metabolised/oxidised in its first passage through the liver after being absorbed, or by a combination of these two mechanisms.
Article
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) produces Parkinsonism in both experimental animals and in man. MPTP is metabolized to 1-methyl-4-phenylpridinium, an inhibitor of mitochondrial complex I. MPTP administration produces ATP depletions in vivo, which may lead to secondary excitotoxicity and free radical generation. If this is the case then agents which improve mitochondrial function or free radical scavengers should attenuate MPTP neurotoxicity. In the present experiments three regimens of MPTP administration produced varying degrees of striatal dopamine depletion. A combination of coenzyme Q10 and nicotinamide protected against both mild and moderate depletion of dopamine. In the MPTP regimen which produced mild dopamine depletion nicotinamide or the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone were also effective. There was no protection with a MPTP regimen which produced severe dopamine depletion. These results show that agents which improve mitochondrial energy production (coenzyme Q10 and nicotinamide) and free radical scavengers can attenuate mild to moderate MPTP neurotoxicity.
Article
Plasma ubiquinol was measured in diabetics, patients on haemodialysis (HD) therapy, patients maintained by continuous ambulatory peritoneal dialysis (CAPD), hyperlipidaemic patients and control subjects. Ubiquinol values were standardized using total cholesterol (mumol/mmol). Diabetics, HD and CAPD patients were found to have plasma ubiquinol levels which were lower than the control subjects. There was no difference in values between the control subjects and hyperlipidaemic patients. Values for diabetics with poor metabolic control were similar to those with good control, and patients with diabetic complications had values which were not significantly different from those for patients with no complications. IDDM patients were found to have values which were lower than the control group, whereas values for the NIDDM patients were not significantly different. These results suggest that increased oxidative stress in certain patient groups may be the result of, and/or the cause of, decreased plasma ubiquinol. This could be due to increased demand or to decreased ability to regenerate the effective form of antioxidant.
Article
Coenzyme Q10 (CoQ10) levels in human plasma were determined by high-performance liquid chromatography (HPLC) with UV detection. CoQ10 was dissociated from lipoproteins by methanol and subsequently cleaned-up on silica gel and octadecyl silica solid-phase extraction cartridges. HPLC separation was performed on a C18 reversed-phase column. The methanol-hexane mobile phase provided a greater possibility of separation procedure adjustment allowing the shortest possible elution time without loss of resolution than a two-alcohol mobile phase. Quantitation was based on the peak heights using a standard addition method. The lower limit of detection was 8 ng on-column, corresponding to 90 micrograms ubiquinone per litre of plasma in an actual sample. Thirty-one randomly selected plasma samples from apparently healthy, 18 to 56-year-old individuals (males and females) were analyzed for total CoQ10. The average level in these subjects was 0.47 +/- 0.18 mg/l with the range of 0.26-1.03 mg/l. The method was also applied to the determination of ubiquinone plasma level changes in one healthy volunteer over a period of one month and after oral intake of CoQ10.
Article
In sperm cells, the majority of coenzyme Q10 (CoQ10) an energy promoting agent and antioxidant, is concentrated in the mitochondria of the midpiece, so that the energy for movement and all other energy-dependent processes in the sperm cell also depend on the availability of CoQ10. The reduced form of CoQ10-ubiquinol also acts as an antioxidant, preventing lipid peroxidation in sperm membranes. The objective of the study was to evaluate the effect of CoQ10 on sperm motility in vitro, after incubation with 38 samples of asthenospermic and normal motility sperm, and to evaluate the effect of CoQ10 administration in vivo in 17 patients with low fertilization rates after in vitro fertilization with intracytoplasmic sperm injection (ICSI) for male factor infertility. All 38 sperm samples from patients registered in our infertility clinic had normal concentrations and morphology. Of these, 16 patients had normal motility (mean 47.5%) and 22 patients were asthenospermic (mean motility 19.1%). Sperm samples were divided into four equal parts and incubated for 24 h in: HAM's medium alone, in HAM's medium with 1% DMSO and HAM's with 5 microM or 50 microM CoQ10. While no significant change in motility after incubation was observed in the samples with initial normal motility, a significant increase in motility was observed in the 50 microM CoQ10 subgroup of sperm from asthenospermic men, with a motility rate of 35.7 +/- 19.5%, as compared to 19.1 +/- 9.3% in the controls (P < 0.05). The 17 patients with low fertilization rates after ICSI were treated with oral CoQ10, 60 mg/day, for a mean of 103 days before the next ICSI treatment. No significant change was noted in most sperm parameters, but a significant improvement was noted in fertilization rates, from a mean of 10.3 +/- 10.5% in their previous cycles, to 26.3 +/- 22.8% after CoQ10 (P < 0.05). In conclusion, the administration of CoQ10 may result in improvement in sperm functions in selective patients. Further investigation into the mechanisms related to these effects is needed.
Article
The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10) in patients with congestive heart failure (CHF) by measuring the possible improvement of certain relevant hemodynamic heart parameters. A statistic aggregation method know as a meta-analysis was used to measure the changes in the cardiac parameters. To begin with we collected the total number of randomized controlled trials and from a total of 14 studies published in the period of 1984-1994, eight studies met our inclusion criteria. The rest were excluded because of a lack of data which made a meta-analysis impossible. The relevant effect parameters investigated were stroke volume (SV), cardiac output (CO), ejection fraction (EF), cardiac index (CI), end diastolic volume index (EDVI), systolic time intervals (PEP/LVET) and total work capacity (Wmax). Seven meta-analyses were performed, one for each of the parameters, and the calculated effect sizes were all positive. Statistical significance could be demonstrated for all of the parameters except the PEP/LVET and Wmax thereby indicating an improvement of greater or lesser magnitude in the CoQ10 group as opposed to the placebo group. Accordingly, the average patient in the CoQ10 group had a better score with regard to SV and CO than 76 and 73% respectively of the patients in the placebo group. In conclusion, supplemental treatment of CHF with CoQ10 is consistent with an improvement of SV, EF, CO, CI and EDVI. Homogeneity could be established for SV and CO. Additional clinical trials of the effect of CoQ10 on CHF are necessary, but, on the basis of the evidence currently available, the possibility remains that CoQ10 will receive a well-documented role as an adjunctive treatment of CHF.
Article
Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.
Article
The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.
Article
Coenzyme Q10 or ubiquinone is a redox component of the respiratory chain, which may be involved in the pathogenesis of cancer. In order to better understand the role of this vitamin in the pathogenesis of breast cancer, a clinical trial including 200 women hospitalized for the biopsy and/or the ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were determined simultaneously with vitamin E plasma concentrations (as antioxidant reference) by HPLC. A coenzyme Q10 deficiency was noted both in carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin E concentrations were within the normal range. A correlation was shown between the intensity of the deficiency and the bad prognosis of the breast disease based on high TNM and SBR values or the lack of estrogen receptors. However, neither cathepsin D level nor adenopathy invasion was related to ubiquinone levels. Since prooxidants may promote tumorigenesis, ubiquinone supplementation in breast cancer could be relevant.
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Coenzyme Q10 and nicotinamide in neural disorders
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