PIPERINE

An active ingredient from various kinds of black pepper. Alongside its own direct anti-inflammatory actions, piperine features in clinical studies alongside other compounds due to its ability to enhance absorption and effect.

In metabolic health, piperine shows evidence of contributing to glucose and cholesterol control alone in some research but more often in combination with curcumin and other supplements including resveratrol. And in systemic inflammatory disease including lupus it has shown beneficial effects with vitamin D+ curcumin. (see References)

Pre-clinical lab studies show promise in direct anti-cancer actions directly and as an adjuvant to chemotherapy. It may increase absorption of some drugs too, so seek qualified medical advice.

 

TYPICAL ABSORPTION LEVELS

10 – 20%

EXAMPLES OF IMPROVED OUTCOMES

PENDING

PRE-DIAGNOSIS OR PREVENTION

NO

Highlighted Studies

Piperine, an alkaloid present in black pepper (Piper nigrum) and long pepper (Piper longum), is known to enhance the bioavailability of a number of therapeutic agents including natural products (15-17). It has been reported that the co-administration of piperine with curcumin enhanced the bioavailability of the latter in rats by 154% and in humans by 2000% probably by reducing the metabolic breakdown rate, increasing the residence time in the intestine, altering the membrane lipid dynamics an...

Link

The measurements of the inflammatory state [with resveratrol and alpha-tocopherol].The observed baseline and post-treatment variations were all beneficial, plasma ferritin levels decreased significantly by 10%, and US CRP [c-reactive protein marker of inflammation] decreased in plasma by 33%, evidencing a highly significant drop; in neutrophils, oxygen consumption decreased by 55% and spontaneous chemiluminescence by 25% after 90 days of treatment; both decreases were highly significant

Link

Serum levels [in non alcoholic fatty liver disease] of FBS [blood sugar levels] significantly declined in case arm in comparison to control arm after the trial timeline… FBS and HbA1c levels were significantly decreased within case individuals in comparison to placebo individuals after the intervention. Levels of HOMA [marker for insulin resistance] were significantly decreased within case group in comparison to control group  after the intervention

Link

We observed that consumption of the dietary supplement [EGCG, capsaicins, piperine and l-carnitine] was associated with a significantly greater decrease in insulin resistance, assessed by homostasis model assessment , leptin/adiponectin ratio , respiratory quotient . LDL-cholesterol levels . Moreover, statistically significant differences were recorded between the two groups in relation to urinary norepinephrine levels. Leptin, ghrelin, C-reactive protein decreased and resting energy expendit...

Link
BACK TO INDEX

TABLE OF REFERENCES

Help grow the evidence. Login and use the form, or try Feedback and Ideas below.

URLRatingHighlightHighlight 2Visuals (click)
https://jgo.amegroups.org/article/view/27856/html3Human studyIn conclusion, the results of the present work support the notion that altered expression of serum IL-10, miR-21, and miR-141 may be prognostic biomarkers that may help to guide treatment in HCC. Further, in a population of patients with fairly advanced HCC, the administration of a combined treatment composed of curcumin, piperine, and taurine for three successive months was able to decrease the circulating level of IL-10 and miR-21, with no effect on miR-141 expression level, which may be reflected on the OS rate positively.The combined treatment was able to decrease IL-10 serum level significantly after 2 cycles of administration which can be attributed to the effect of the treatment on the signal transducer and activator of transcription3 (STAT3) which is a pro-inflammatory transcription factor known to be constitutively expressed and play a major role in the pathogenesis of several cancer types (46). In cancer cells, STAT3 promotes the expression of factors that are both immunosuppressive and STAT3 activating, including vascular endothelial growth factor (VEGF) and IL-10. These tumor-derived factors, in turn, up-regulate STAT3 signaling in various immune-cell subsets in the tumor microenvironment, which produce more immunosuppressive factors, including IL-6, IL-10, transforming growth factor-β (TGF-β), and VEGFScreenshot from 2024-04-02 16-19-59
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602615/3Human study..we used a biopower formula containing three active ingredients: Resveratrol + Piperine + Alpha-Tocopherol (FRAMINTROL®) in the management of patients with Metabolic Syndrome. The results of this treatment evidenced a significant decrease in plasma ferritin levels and a highly significant decrease in US-CRP levels..Plasma ferritin and US CRP might be good biomarkers of inflammation for the clinical follow up of patients with MetS..A highly significant decrease in the oxygen consumption and spontaneous chemiluminescence of polymorphonuclear cells might be indicative of a remarkable drop in the proinflammatory metabolism of these cells of the immune system and of decreased levels of oxidant reactive species..Reducing chronic inflammation in MetS patients should be a new prevention goal to decrease CVD risk factors.Piperine is a bioactive alkaloid that gives black pepper its pungency. It has a broad spectrum of action in molecular biology, as an antioxidant, anti-inflammatory, antiangiogenic, antibacterial and immunomodulatory agent. Piperine may be naturally extracted from black pepper, with a 6% to 13% yield. Despite its many healthy properties, the use of piperine in human health is still limited due to its scarce availability and low solubility in water [40,41]. However, piperine has been shown to be a resveratrol booster, since the oral administration of a formula of piperine plus resveratrol (10/100 mg/kg, respectively) increases the bioavailability of resveratrol by 1544% when compared to resveratrol alone [42]. Alpha-tocopherol has been shown to have anti-inflammatory effects due to the decreased production of anti-inflammatory cytokines IL-1 beta IL-6 and chemokine IL-8, together with the neutralization of alpha-TNF [43]. In obese individuals with and without diabetes, MetS is related to chronic systemic inflammation and low levels of alpha-tocopherol
https://www.nature.com/articles/s41598-024-51726-z#2Human studyThey were prescribed a placebo and 5 mg of piperine for 12 weeks, respectively. The demographic and laboratory parameters of individuals were assessed as the baseline and after the duration of piperine intake. Piperine with a daily dosage of 5 mg could significantly decrease hepatic enzymes and glucose, and alleviate dyslipidemia in the case arm rather than the control arm. Moreover, HOMA levels and insulin resistance were reduced in case participants compared to the control counterparts.Piperine could significantly reduce hepatic enzymes, and ameliorate lipid and glucose metabolisms in this study. Piperine could also reduce insulin resistance and HOMA levels within case group compared with control group. Piperine exerts its favorable action in insulin resistance and hepatic steatosis through impairment of Lxr-α, Srebp1c, CD36, Chrebp-α, and Fas in high-fat diet mice model39. Piperine can also reduce the levels of hepatic lipogenesis via inducing the transporter protein of ATP binding cassette sgm8 (Abcg8) and hepatic scavenger receptor b1 (Sr-b1) in small intestine of high-fat diet mic
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790246/2Human studyIn fact, when comparing the effect of the dietary supplement with that of the placebo in our study, we observed that consumption of the dietary supplement was associated with a significant decrease in insulin resistance (assessed by HOMA and QUIKI), leptin/adiponectin ratio, RQ and LDL-cholesterol levels. Leptin, ghrelin and CRP significantly decreased in the supplemented group but not in the placebo group, whilst adiponectin levels significantly decreased in the placebo group but not in the supplemented group, although no statistically significant difference between the groups was recorded. This framework constitutes a significant improvement in the metabolic status of the supplemented patients, especially in light of the fact that weight loss does not always lead to an improvement in a patient’s inflammatory state and insulin resistanceSeveral spices have been shown to exhibit activity against obesity through their antioxidant and anti-inflammatory mechanisms [24]. Of these, in addition to EGCG, capsaicin has been investigated most extensively as an antioxidant agent [25]. The use of capsaicin has therefore been investigated as a treatment for obesity and obesity-related metabolic diseases, as well as for its thermogenic activity [26–30] and its satiating effect [31, 32]. Piperine is an active component of black pepper that can effectively suppress lipid peroxidation [33, 34] and enhance the bioavailability of curcumin and other substances through the inhibition of drug-metabolizing enzymes in the liver
https://www.eurekaselect.com/article/1382372Human studyAlthough vitamin D or curcumin-piperine alone could improve the clinical outcome and cytokines levels in SLE, curcumin-piperine combined with vitamin D had the best outcome in improving the disease activity and cytokines levels among patients with SLE.Mex-SLEDAI, FSS, and IL-6 were reduced significantly, while TGF-β serum levels were increased in all groups after the treatments (p <0.05). Changes in Mex-SLEDAI score (p = 0.003 and p = 0.008), FSS (p = 0.001 and p <0.001), and TGF-β (p = 0.003 and p = 0.004) serum levels were significantly higher in group III compared to the group I or group II.
https://brieflands.com/articles/jjnpp-136383.pdf2Human study[curcumin+ginger+piperine] curcumex supplement in patients with type 2 diabetes decreases BMI and blood sugar indicators, including serum levels of HbA1C, insulin, HOMA-IR, and fasting blood sugar, but had no effect on the lipid profile of these patients. Considering the effectiveness of this supplement and its low complication rate (in this study, no specific side effect was reported by its users), it can be used in newly diagnosed type 2 diabetic patients (for whom lifestyle modification alone cannot lead to proper disease control). It can also be recommended for patients who use one or two oral antihyperglycemic drugs and still have not achieved proper control of glycemic indices, and especially patients who have a high BMI can benefit more.Accordingly, it can be concluded that the mixture of the three mentioned supplements should have significant beneficial effects in controlling glycemic indices and lipid profiles in type 2 diabetic patients. A subject that was proven at least in part during the present study. Fasting blood glucose, HBA1C, insulin resistance, and BMI are among the indicators that showed a significant decrease in the group receiving the supplement at the end of the study compared to baseline, which was not observed in the placebo group
https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0040-1722808.pdf1Lab study- adjunct The mechanism of synergistic action after the treatment with piperine and radiation may be due to enhanced DNA damage and cell cycle arrest through induction of ROS that may alter mitochondrial membrane potential leading to apoptosis as observed in our earlier studies with colon cancer cells26 and other cancer cell line studies.40 These findings have unique significance, as piperine may have the potential to be developed as a radiosensitizing against lung cancer cells.Piper nigrum Linn commonly known as black pepper belongs to the spices widely consumed by a great number of people worldwide. Piperine is a bioactive compound and key alkaloid, present in Piper nigrum Linn and Piper longum Linn (long pepper). It has been found that piperine enhances the action of the anticancer drugs in various drug-resistant cancer cells.Screenshot from 2023-06-02 13-36-43
https://www.nature.com/articles/aps20112091Lab studyPiperine can inhibit tumor growth by inducing cell apoptosis and cell cycle blockage. Also it can suppress 4T1 tumor growth and metastasis in vivo. Further studies will need to be carried out to determine the exact mechanisms of the antitumor action of piperine, and to investigate how it can be used in cancer therapy alone or combination with other antitumor drugs.t is...Metastasis requires the degradation of ECM molecules in the basement membrane, which is the largest barrier between cancer cells and the bloodstream. The key proteases that are involved in ECM degradation contain MMPs. Our results showed that Piperine significantly reduced the mRNA expression of MMP-9 and MMP-13. It had been reported that suppression of the expression of MMP-9 in tumor cells by piperine is through the inhibition of PKCα and ERK phosphorylation and reduction of NF-κB and AP-1 activationScreenshot from 2023-06-02 13-25-592.5 and 5mg/kg
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784594/1Lab studyPiperine inhibits proliferation and induces apoptosis in human gastric cancer, which is associated with the upregulated protein expression of Bax, Bad, Cyto C, cleaved PARP, and cleaved caspase-3, and the downregulated protein expression of Bcl-2 and Bcl-xl. In addition, the anti-cancer mechanism of piperine in the gastric cancer cell line SNU-16 may be realized by inhibiting the PI3K/Akt pathway. In summary, piperine may be an effective chemotherapeutic agent against gastric cancer.An in vivo study revealed that, compared with the control group, the tumor volume of mice treated with piperine was significantly reduced. Piperine enhanced cleaved caspase-3 expression but decreased Ki-67 expression in a dose-dependent manner. Moreover, the nontoxicity effect of piperine was confirmed by H&E staining analysis in kidney and heart tissues of mice.Screenshot from 2023-11-22 14-24-0030 and 60mg/kg
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323232/1Lab study- adjunct Hence, we can state that PIP inhibits survivin at a very low concentration and increases the efficacy of the standard of care drugs. We also found that the combination has a very significant effect on the viability of both P (Figure 12A) and S cell pools (Figure 12B) where the single drug has very little effect. The CI value of the combination is indicated on top of the graph of P cells. This indicates the involvement of survivin in resistance to first line therapy.Piperine at very Low Concentration Inhibits Survivin in Both P and S Cells To identify the inhibitory effect of PIP in the cell line, we treated the cells with 25 µM (~ IC10) PIP for 48 h. The concentration was selected based on the IC50 value of PIP, which was 120 µM (Figure 11A). After this, both the treated and control cells were analyzed for the expression of survivin, using both IHC and RT-PCR. The gene expression analysis showed around 75% reduction in survivin expression in the S population and about 50% in the P cells (Figure 11C). The IHC results were also similar to this (Figure S4). Our results pointed towards the potential Piperine as an inhibitor of survivin in both GBM and GSCs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385350/1Lab study Furthermore, piperine was more active in cells with an aggressive phenotype, and possibly its mechanism of action involves cell migration and invasion pathways. This finding demonstrates for the first time the relationship between piperine cytotoxic activity and the phenotype of the gastric cancer lineages. Additionally, the results showed that besides acting in isolation on cancer models, when tested in combination, piperine provides considerable improvement in the activity of commercial chemotherapeutics such as 5-Fluorouracil and Gemcitabine, which is a very promising finding with possible outcomes in future research and clinical endeavors. This action leads to a decrease in the effective concentration of chemotherapeutic drugs on cells, which may mean more effective therapeutic perspectives and a reduction in toxicitychemotherapeutic systems combined with piperine are effective in the cytotoxicity of tumor cells, generating increased absorption and therapeutic efficacy of the drugs and allowing lower concentrations to produce the same or even improved effects [71,110,111]. This trend endorses our findings in gastric cancer models since piperine enhanced the activity of the tested chemotherapeutic drugs, decreasing their required effective concentrations in vitro. Because piperine exhibits multiple mechanisms in gastric cancer cells, its enhancing ability may still bring other benefits in the search for more effective treatments.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2688199/1Lab studyWe found that piperine significantly inhibited the production of two important proinflammatory mediators, IL6 and PGE2, in IL1β-stimulated human FLS. This result was consistent with other studies that showed potent anti-inflammatory effects in other systems. The inhibition of PGE2 production is important due to its central role in triggering pain. In addition, MMP1 and MMP13 collagenases play dominant roles in RA and osteoarthritis because they are the rate-limiting components of the collagen degradation process. The significant inhibition of MMP13 expression is particularly important because it degrades a wide range of collagenous and non-collagenous extracellular matrix macromolecules and is remarkably active against collagen type II, the predominant collagen in cartilage. To our knowledge, this is the first report to show that piperine inhibited the expression of MMP13 in IL1β-stimulated FLSs.Piperine is also known to enhance the bioavailability of some drugs by inhibiting drug metabolism or by increasing absorption [18,24,26]. Thus, piperine may prove to be useful on combination treatments with other drugs. For example, a combination of gallic acid and piperine reduced beryllium-induced hepatorenal dysfunction and the associated oxidative stress [22]. In addition, a synergistic effect of piperine was demonstrated in a clinical study that tested the pharmacokinetics of nevirapine, a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase [27]. The combination therapy was well tolerated, with few or no clinical adverse effects, and the mean maximum plasma concentration of nevirapine was increased when combined with piperine

Help grow the community

Join the Pubmedders subscriber base

Get our monthly email newletter – designed so you can give us your opinions, thoughts and feedback…

ALL contributions are invested into growing the site to help others.