You Eat Peppers Daily, But You Might Not Know All 10 Benefits Just Through Theirs Bioactive Phytochemical Piperine

By Kyle J. Norton

Phytochemicals, the natural chemical constituent, protect the plants against diseases and form their outer's color. Phytochemicals may be next potential sources of new medicine for treatment of diseases with little or no side effects.

Piperine is a phytochemical alkaloid in the class of organosulfur compound, found abundantly in white and black pepper, long pepper, etc.

1. Antimicrobial activity

The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases. 

The immune system does a great job of keeping people healthy and preventing infections. Beside foods and nutritional supplements, herbs also play a important role in helping the immune system defend against viruses and bacteria attacks.

In the study of piperine combination with mupirocin for antimicrobial activity against Staphylococcus aureus strains including meticillin-resistant S. aureus, the combination showed more effective against the tested subject when compared with the commercially available formulation of 2 % mupirocin alone(1). Other in the study of the same subject showed the enhanced accumulation and decreased efflux of ethidium bromide in the wild-type and mutant (CIPr-1) strains in the presence of piperine(2).

2. Breast Cancer

Breast cancer (malignant breast neoplasm) is an abnormal cells growth disoerderly and uncontrolably in the breast tissue, either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. 

. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.

Piperine, a chemical component of black pepper, showed a strongly inhibited proliferation and induced apoptosis of breast caner cells and HER2 (Human epidermal growth factor receptor 2, HER2-positive breast cancer tends to be more aggressive) gene expression. Pretreatment of piperine also enhanced sensitization to paclitaxel killing in HER2-overexpressing breast cancer cells of that reduces the risk of cancer from occurring(3). 

Other study of piperine against breast cancer also showed that Piperine (35-280 μmol/L) inhibited the growth of 4T1 cells in time- and dose-dependent manners (the IC(50). Treatment of 4T1 cells with piperine(70-280 μmol/L) induced apoptosis of 4T1 cells, accompanying activation of caspase 3. As the results, the phytochemical piperine may be a potential agent for treating breast cancer(4).

3. Angiogenesis

Angiogenesis is the action in stimulated production of new blood vessels to support the growth and cells.

Piperine, a major alkaloid constituent of black pepper, exerted it anti angiogenic effect to cause apoptosis in some cancer cell lines such as in inhibited the proliferation and G(1)/S transition of human umbilical vein endothelial cells (HUVECs) without causing cell death, as well as collagen-induced angiogenic activity by rat aorta explants and breast cancer cell-induced angiogenesis in chick embryos(5). Piperine in the co administration with curcumin, enhancing the functions of curcumin in suppression of many diseases including angiogenesis(6).

4. Cognitive Impairment

Cognition is the process of the brain including the attention of working memory, producing and comprehending language, learning, reasoning, problem solving, and decision making.

In chronic unpredictable stress (CUS)-induced cognitive impairment and oxidative stress in mice,
Piperine showed to potentiate the protective effects of curcumin in significantly improved behavioral and biochemical alterations, restored mitochondrial enzyme complex activities and attenuated increased acetylcholinesterase and serum corticosterone levels(7).

 In olfactory bulbectomy induced depression in rats, co-administration of piperine with curcumin significantly potentiated the effects in behavioral, biochemical, mitochondrial, molecular and histopathological alterations(8). 

These potentiation of co administration also showed to prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol, as compared to their effects alone(9). 

5.  Obesity's Inflammatory Metabolic Dysfunctions

Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.

Study of combination of bioactive food ingredients, including piperine in Forty-one patients and 45 patients in control group, showed a significantly greater decrease in insulin resistance, with leptin, ghrelin, C-reactive protein decreased and resting energy expenditure increased significantly in the supplemented group compared to the placebo(10). 

In mice fed with high fat diet-induced hepatic steatosis, administration of piperine (50 mg/kg body weight) significant increased in plasma adiponectin levels, induced elevated plasma concentrations of insulin and glucose. Piperine also reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK)( a metabolic enzyme in controls a number of metabolic pathways) signalling molecules linking to lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice(11). 

Also in Male Wistar rats fed with high fat diet study, piperine supplementation also improved the plasma levels of apo A-I, T3, T4, testosterone, and I and significantly reduced apo B, TSH, and insulin to near normal levels(12).

6. Diabetes

Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

Administration of piperine isolated from the fruits of Piper nigrum crude extract diabestes induced in albino mice using alloxan, showed the crude extract exhibit its anti-diabetic effect inducing a significant blood glucose lowering at dose of 20 mg/kg on day 14(13). 

In other alloxan-induced diabetic models study, piperine (10 mg/kg) significantly increased the dose-dependent anti-hyperglycemic activity of nateglinide(a drug for the treatment of type 2 diabetes), leading to synergistic anti-hyperglycemic activity of the diabetic medicine(14). 

In diabetes-induced oxidative stress in 30-day streptozotocin-induced diabetic Sprague-Dawley rats, piperinetreatment (10 mg/kg/day, intraperitoneally for 14 days) reversed the diabetic effects on oxidized glutathione concentration in brain, on renal glutathione peroxidase and superoxide dismutase activities, and on cardiac glutathione reductase activity and lipid peroxidation(15).

7. Allergic Effect

The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases. 

The immune system does a great job of keeping people healthy and preventing infections.

In picryl chloride (PC)-induced ear swelling in PC sensitized mice, PN-ext exhibited its histamine release inhibitory activity, in vitro on compound 48/80-induced histamine release from rat peritoneal mast cells(16). 

Piperine(4.5 and 2.25 mg/kg) orally administered 5 times a week for 8 weeks in a murine model of asthma, showed an effectiveness in suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness by sinduced the production of interleukin-4, interleukin-5(white blood cells expression), immunoglobulin E and histamine(17).

8. Immunity

Ethanolic extract of fruits of Piper longum L.(PLE) and piperine was found to inhibit the lethal action of venom both in the in vitro lethality neutralization assay and in vivo lethality neutralization assay against Russell's viper venom in mice by enhancing production of antigen and antibodies response(18).

In the study of the same subject, administration of PLE and piperinesignificantly (p<0.01) inhibited venom induced lethality, haemorrhage, necrosis, defibrinogenation and inflammatory paw edema in mice in a dose dependent manner, reduced venom induced mast cell degranulation in rats(19).

9. Asthma

Asthma is a chronic inflammatory disease affecting the air way of the lung with recurring symptoms, such as wheezing, chest tightness, shortness of breath, and coughing.

Study of bacterial infections causes of frequent respiratory infections, including bacterial infections provoke asthma attack, showed a positive effect of Piper Longum L. Extract (20% Piperine) in exhibition of a moderate activity antibacterial activity against selected strains, such as Haemophilus influenzae , Streptococcus pneumoniae , Streptococcus pyrogene and Staphylococcus aureus(20).

 In the study of antioxidant defenses of asthma patient, Piper longum extract (20% Piperine) showed a potent antioxidant activiy by scavenging Nitric oxide to prevent the bronchial inflammation in asthmatic patients(21).

The information finding, suggested that peppers including white and black pepper and thier major bioactive compound may be considered as function food for prevention and treatment of ailments indicated above. However, intake of pepper supplement should be taken with care in prevention of acute liver toxicity.

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References
(1) Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus by Mirza ZM, Kumar A, Kalia NP, Zargar A, Khan IA.(PubMed)
(2) Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus by Khan IA, Mirza ZM, Kumar A, Verma V, Qazi GN.(PubMed)

(3) Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells by Do MT, Kim HG, Choi JH, Khanal T, Park BH, Tran TP, Jeong TC, Jeong HG.(PubMed)
(4) Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model by Lai LH, Fu QH, Liu Y, Jiang K, Guo QM, Chen QY, Yan B, Wang QQ, Shen JG.(PubMed)

(5) Piperine, a dietary phytochemical, inhibits angiogenesis by Doucette CD, Hilchie AL, Liwski R, Hoskin DW.(PubMed)
(6) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature by Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB.(PubMed)

(7) iperine potentiates the protective effects of curcumin against chronic unpredictable stress-induced cognitive impairment and oxidative damage in mice by Rinwa P, Kumar A.(PubMed)
(8) Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression by Rinwa P, Kumar A, Garg S.(PubMed)
(9) Protective effect of curcumin and its combination with piperine(bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence by Bishnoi M, Chopra K, Rongzhu L, Kulkarni SK.(PubMed)

(10) Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects by Rondanelli M, Opizzi A, Perna S, Faliva M, Solerte SB, Fioravanti M, Klersy C, Cava E, Paolini M, Scavone L, Ceccarelli P, Castellaneta E, Savina C, Donini LM.(PubMed)
(11) Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice by Choi S, Choi Y, Choi Y, Kim S, Jang J, Park T.(PubMed)
(12) Piperine, an active principle from Piper nigrum, modulates hormonal and apo lipoprotein profiles in hyperlipidemic rats by Vijayakumar RS, Nalini N.(PubMed)

(13) Evaluation of the effect of piperine per se on blood glucose level in alloxan-induced diabetic mice by Atal S, Agrawal RP, Vyas S, Phadnis P, Rai N.(PubMed)
(14) Effect of piperine on antihyperglycemic activity and pharmacokinetic profile of nateglinide by Sama V, Nadipelli M, Yenumula P, Bommineni MR, Mullangi R.(PubMed)
(15) Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats by Rauscher FM, Sanders RA, Watkins JB 3rd.(PubMed)

(16) Histamine release inhibitory activity of Piper nigrum leaf by Hirata N, Naruto S, Inaba K, Itoh K, Tokunaga M, Iinuma M, Matsuda H.(PubMed)
(17) Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma model by Kim SH, Lee YC.

(18) Production of high titre antibody response against Russell's viper venom in mice immunized with ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine by Shenoy PA, Nipate SS, Sonpetkar JM, Salvi NC, Waghmare AB, Chaudhari PD.(PubMed)
(19) Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) against Russell's viper venom: characterization of piperine as active principle by Shenoy PA, Nipate SS, Sonpetkar JM, Salvi NC, Waghmare AB, Chaudhari PD.(PubMed)

(20) Effect of selected antiasthmatic plant constituents against micro organism causing upper respiratory tract infection by Nilani P, Duraisamy B, Dhamodaran P, Ravichandran S, Elango K.(PubMed)
(21) Invitro antioxidant activity of selected antiasthmatic herbal constituents by Nilani P, Kasthuribai N, Duraisamy B, Dhamodaran P, Ravichandran S, Ilango K, Suresh B.(PubMed)