# Pippali

> Pippali (Piper longum) is classified in Ayurveda as Deepaniya (Appetizer), Rasayana, from the Piperaceae family. Parts used: fruit, root. Unique in Ayurveda for Rasayana through Vardhamana (graduated dosing). Listed in the Ayurvedic Pharmacopoeia of India (API), Part I, Volume I, Monograph No.

## Key facts

- **Botanical name:** Piper longum
- **Family:** Piperaceae
- **Ayurvedic category:** Deepaniya (Appetizer), Rasayana
- **Pharmacopoeia status:** Listed in the Ayurvedic Pharmacopoeia of India (API), Part I, Volume I, Monograph No. 4, published by Department of AYUSH, Ministry of Health & Family Welfare, Government of India. Recognized in multiple traditional pharmacopeias across South and Southeast Asia. No dedicated WHO monograph. Widely used in Ayurvedic compound formulations (e.g., Trikatu).

## Names and identification

| Language | Name |
|----------|------|
| English | Pippali |
| Common Names | Long Pepper, Indian Long Pepper |
| Hindi | Pippal, Pippali |
| Sanskrit | Pippali, Magadhi |
| Latin/Botanical | *Piper longum* |

## Parts Used

- Fruit
- Root

## Dosha Effects

| Dosha | Effect |
|-------|--------|
| **Vata** | Decreases |
| **Kapha** | Decreases |
| **Pitta** | Increases |

## Key Phytochemical Constituents

- [Piperine](/reference/piperine/)
- [Piperlongumine](/glossary/compounds-o-q/#piperlongumine)
- [Pipernonaline](/glossary/compounds-o-q/#pipernonaline)
- [Sesamin](/glossary/compounds-q-t/#sesamin)
- [Piperlonguminine](/glossary/compounds-o-q/#piperlonguminine)

## Therapeutic Actions (Karma)

- Bioavailability enhancer
- [Bronchodilator](/reference/bronchodilator/)
- Digestive stimulant
- Immunomodulator
- [Hepatoprotective](/reference/hepatoprotective/)
- Rejuvenative

## How does it work?

- Piperine inhibits CYP450 [enzymes](/glossary/compounds-d-g/#enzymes) (especially CYP3A4) and UDP-glucuronosyltransferase, reducing first-pass metabolism and enhancing bioavailability of co-administered compounds.
- Piperine directly activates TRPV1 (capsaicin receptor) by binding to the capsaicin-binding pocket but in different poses than capsaicin, making it a weak agonist with distinct structural mechanism.
- Piperine interacts with T671 on the pore-forming S6 segment of TRPV1 to induce channel opening.
- Piperlongumine (from Piper longum) acts as a senolytic agent: selectively kills senescent cells by targeting OXR1 (Oxidation Resistance 1), binding directly and inducing its degradation via the ubiquitin-proteasome system in a senescent cell-specific manner.
- Piperlongumine acts as allosteric antagonist of TRPV2 channel, impairing glioblastoma cell survival.
- Piperlongumine induces apoptosis in senescent cells without requiring reactive oxygen species induction.
- Piperine inhibits P-glycoprotein efflux transporter, further enhancing intestinal drug absorption.

## How is it used traditionally?

Component of [Trikatu](/herb/trikatu/). Unique in Ayurveda for Rasayana through Vardhamana (graduated dosing). Enhances bioavailability of other herbs. Used for Shwasa (asthma), Kasa (cough), and Agnimandya (weak digestion).

## Where is it described in the classical texts?

- Charaka Samhita (Deepaniya group)
- Sushruta Samhita
- Bhavaprakasha Nighantu

## What do recent clinical trials show?

- Shah SB, Guttal GK, Chikkanna U and others 2022. [Efficacy of Pippali in vardhamana and fixed dosage pattern in primary hypothyroidism - A randomized clinical trial](https://pubmed.ncbi.nlm.nih.gov/35661936/). *Journal of Ayurveda and integrative medicine*. PMID [35661936](https://pubmed.ncbi.nlm.nih.gov/35661936/) · [doi:10.1016/j.jaim.2022.100555](https://doi.org/10.1016/j.jaim.2022.100555)  
  Published in J Ayurveda Integr Med, this RCT evaluated Pippali in graduated (vardhamana) versus fixed dosage patterns for primary hypothyroidism management.
- Bailey HH, Johnson JJ, Lozar T and others 2021. [A randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrol](https://pubmed.ncbi.nlm.nih.gov/32868637/). *European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)*. PMID [32868637](https://pubmed.ncbi.nlm.nih.gov/32868637/) · [doi:10.1097/CEJ.0000000000000621](https://doi.org/10.1097/CEJ.0000000000000621)  
  Published in Eur J Cancer Prev, demonstrated piperine's bioavailability-enhancing effects on [resveratrol](/glossary/compounds-q-t/#resveratrolresveratrol) serum levels in a dose-ranging clinical trial.
- Biswas P, Ghorai M, Mishra T and others 2022. [Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health-promoting activities](https://pubmed.ncbi.nlm.nih.gov/36256521/). *Phytotherapy research : PTR*. PMID [36256521](https://pubmed.ncbi.nlm.nih.gov/36256521/) · [doi:10.1002/ptr.7649](https://doi.org/10.1002/ptr.7649)  
  Comprehensive review cataloguing [analgesic](/reference/analgesic/), carminative, anti-diarrhoeic, immunostimulant properties and applications in asthma, insomnia, dementia, epilepsy, diabetes, and rheumatoid arthritis.
- Conde J, Pumroy RA, Baker C and others 2021. [Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression](https://pubmed.ncbi.nlm.nih.gov/34079902/). *ACS central science*. PMID [34079902](https://pubmed.ncbi.nlm.nih.gov/34079902/) · [doi:10.1021/acscentsci.1c00070](https://doi.org/10.1021/acscentsci.1c00070)  
  Piperlongumine binds to a transient allosteric pocket on hTRPV2, demonstrating a new mode of [anticancer](/reference/anticancer/) activity against glioblastoma where TRPV2 is overexpressed.

*2 further claims previously listed here could not be traced to a published paper and have been removed. An absence here means we could not identify the source, not that no work exists.*

## Recent safety updates

- Piperine inhibits CYP3A4 and increases AUC of multiple drugs: simvastatin (+59%), alfentanil (+39%), triazolam (+36%), cyclosporine (+35%), nifedipine (+34%), ritonavir (+31%), itraconazole (+24%), midazolam (+20%), clarithromycin (+17%), carbamazepine (+11%).
- Piperine may inhibit P-glycoprotein (PGP), increasing fexofenadine bioavailability.
- Interactions in humans observed at bolus doses of 20 mg piperine/day; doses as low as 5 mg/day may cause interactions with certain substances.
- Dose-dependent toxicity concerns: poor water solubility limits safe high-dose administration.
- Animal studies indicate disturbance of spermatogenesis at higher piperine bolus doses.
- Animal studies show maternal reproductive and embryotoxic effects at higher doses.
- Hepatic concerns at high doses in animal models.
- As a potent bioavailability enhancer, any co-administered medication dosing should be reviewed - piperine can significantly alter pharmacokinetics of co-administered drugs.

## Recommended Dosage

Fruit powder: 1-3g/day; Vardhamana Pippali (graduated dosing): as per classical protocol

## Safety, contraindications and cautions

- Pitta disorders
- Gastritis/ulcers
- Pregnancy
- May enhance drug absorption (interaction concern)

## What is it made of?

**Part(s) Analyzed:** Fruit, Root

### Alkaloids (Piperidine)

- Piperine (4-9%)
- Piperlongumine
- Piperlonguminine
- Pipernonaline
- Retrofractamide A-C

### Lignans

- Sesamin
- Pluviatilol

### Volatile Compounds

- Caryophyllene
- Pentadecane
- Bisdemethoxycurcumin

### Essential Oil Composition

- **Caryophyllene:** 18-25%
- **Pentadecane:** 8-12%
- **Bisabolene:** 5-8%
- **Thujene:** 3-5%
- **Terpinolene:** 2-4%

**Analytical Methods:** HPLC-UV (piperine), GC-MS (essential oil), UV spectrophotometry

## Dosage forms and preparation

**Dosage Forms:** Churna (powder), Capsule, Tablet, Avaleha (confection), [Ghrita](/herb/ghrita/) (medicated ghee), Rasayana formulation, Vardhamana Pippali (graduated dose protocol), Honey-based preparation

**Standard Dosage:** 250-500 mg powder 1-3 times daily; 125-500 mg standardized extract twice daily; Vardhamana protocol: start 1 fruit, increase by 1 daily to 10, then taper

**Bioavailability:** Piperine from Pippali (Piper longum) has excellent oral bioavailability (>90%) and is itself a potent bioenhancer. Piperlongumine shows moderate bioavailability (~35-50%) with rapid absorption. Piperine inhibits CYP3A4, CYP2D6, and P-glycoprotein, significantly enhancing bioavailability of co-administered compounds ([curcumin](/herb/curcumin/) bioavailability increased 20-fold). Piperine also inhibits UDP-glucuronosyltransferase, reducing Phase II metabolism of many phytochemicals.

**Optimal Timing:** Before meals with honey for respiratory conditions. With meals or after meals for digestive purposes. As bioenhancer: taken simultaneously with the compound being enhanced.

**Standardized Extract:** Pippali fruit extract standardized to piperine >5% (general supplement) or >95% (bioenhancer isolate). Piperlongumine-enriched extract >2%. Full-spectrum extract (4:1) with piperine >3% and total piperamides >8%.

**Shelf Life:** Dried fruit: 24-36 months; Churna: 18-24 months; Standardized extract: 24-36 months; Piperine isolate: 36-48 months; [Ghrita](/herb/ghrita/): 24-36 months

**Storage:** Dried fruit and powder: airtight containers, below 25 deg C, RH <55%, protected from light (piperine photodegradation). Piperine isolate: amber glass, desiccated, 2-25 deg C. Ghrita: clean, dry containers, below 30 deg C.

**Marker Compounds:** Piperine, Piperlongumine, Piperlonguminine, Pipernonaline, Retrofractamide A, [Pellitorine](/glossary/compounds-o-q/#pellitorine), Sesamin, Beta-[sitosterol](/glossary/compounds-q-t/#sitosterol)

### Extraction Methods

- Fine powdering of dried fruit (traditional Churna)
- Hydroalcoholic extraction (70-80% ethanol) for piperine-rich extract
- Supercritical CO2 extraction for high-purity piperine
- Ethanol extraction followed by crystallization for piperine isolation
- Oil extraction (Ghrita Paka) in ghee base

### Synergistic Combinations

- [Haridra](/herb/haridra/)/[Curcumin](/herb/curcumin/) (20-fold bioavailability enhancement)
- [Ashwagandha](/herb/ashwagandha/) (Rasayana combination with enhanced withanolide absorption)
- [Trikatu](/herb/trikatu/) combination (Pippali + Maricha + Shunthi for digestive fire)
- [Sitopaladi Churna](/formulation/sitopaladi-churna/) (respiratory health formulation)
- [Chyawanprash](/formulation/chyawanprash/) (key ingredient in classical Rasayana)

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Canonical version of this page: https://nighantu.ageayurveda.com/herb/pippali/

## Sources

- Amidha Ayurveda Herb Database (700+ herbs, CC-BY-4.0)
- AgeAyurveda Product Catalog
- Classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Bhavaprakasha Nighantu, Ashtanga Hridaya)
- Web research (clinical trials, WHO monographs, safety databases)
- Ayurvedic Pharmacopoeia of India

Published by Age Ayurveda in the Nighantu. Educational reference only, not medical advice.
Incorporates material from the Amidha Ayurveda Herb Database under CC BY 4.0.