Piperlongumine: A Natural Senolytic in the Spice Pippali (Long Pepper)

Another natural senolytic compound has since been discovered: piperlongumine, found concentrated in a spice sold in Indian grocery stores, known as “pippali.” There are thousands of different plants in the black pepper family (distinct from the few dozen or so species in the chili pepper family). The two most commercially important ones are Piper nigrum, which is plain black pepper, and Piper longum, known as pippali in India, pibo in Chinese, and long pepper in Europe. Pippali is more pungent than black pepper and has a sweet, hot, numbing taste.

For over 2000 years, pippali was one of the most valuable Indian exports as both a food and a medicine. (Hippocrates considered it the latter rather than the former.) It’s mentioned in ancient Ayurvedic texts dating back 6000 years and has been included as an ingredient in hundreds of herbal remedies, most notably trikatu, a Sanskrit word meaning “three acrids,” trikatu is a mixture of black pepper, pippali, and ginger in equal proportion.

Traditionally, pippali was used for everything from leprosy and gonorrhea to paralysis of the tongue, evidently possessing “good anti-snake venom properties.” A modern pharmacologic analysis identified 20 drug-like phytochemicals in the spice, including the senolytic piperlongumine.

Most of the interest in piperlongumine to date has been in oncology after it was found to selectively kill off several different types of cancer, but that was in vitro, or in xenografts where, for example, piperlongumine treatment could shrink human breast cancer tumors implanted in mice by more than 50 percent within three weeks. No clinical cancer trials have been published to date, though.

Pippali has evidently been tested on patients with respiratory disorders and childhood asthma, reported to successfully decrease the severity of asthma attacks by more than 50 percent. This is not surprising given its anti-inflammatory properties that are as strong or stronger than anti-inflammatory prescription drugs in preclinical studies. Piperlongumine has been shown to improve cognitive function in aged mice, but its anti-aging potential has yet to be tested in people.

Unfortunately, the bioavailability of piperlongumine has yet to be calculated; so, we don’t know how much pippali one would have to eat to reach the senolytic dose in our tissues. I love spicy food, so was excited to add it to my tabletop armamentarium, figuring why not? Pippali is widely used in cooking, so is generally assumed to be safe in culinary doses. It has been shown to have contraceptive properties in animals, though, and so, its use during pregnancy and breastfeeding is not recommended.