Piperine

Piperine Update Report

Amala Soumyanath’s personal history with black pepper, piperine, and Vitiligo.

Piperine was discovered as a viable treatment for vitiligo according to Amala Soumyanath’s research. She presents the narrative from her own perspective and keeps us up to date on the latest developments:

My First Introduction to Vitiligo: A Personal Passion

My vitiligo journey began on a regular working day nearly 20 years ago! I worked as a faculty member in the Department of Pharmacy at King’s College London as a registered pharmacist with a Ph.D.

In my favorite topic, pharmacognosy, the scientific study of therapeutic compounds found in nature, I taught courses and directed a research group. I received a call from a “Maxine Whitton of the Vitiligo Society” one day out of the blue. She explained that a member had gotten a Chinese herbal prescription with numerous identified plants and asked if I could check to see if any of them were estrogenic. I promised to assist, but the first thing I had to do was Google “vitiligo”! I was shocked to learn that vitiligo was the name of a skin condition that I had seen in several people. The ailment is marked by patches of depigmented skin, and I was previously familiar with it as “oeleucoderma.” I was instantly attracted by the disease, its etiology, and the fact that PUVA therapy for vitiligo was based on psoralens, which are produced from plants, as a pharmacist and scientist studying medicinal plants. I also discovered that there was no truly effective vitiligo treatment. I resolved right then and there that I would utilize my scientific skills to look for a new therapy, starting with plants used in traditional herbal medicine. I had no idea that I would acquire vitiligo myself, turning my hunt for a remedy into more than a fun study project.

Piperine’s Discovery

The first step was to do research and establish a list of herbs used to treat vitiligo in various herbal medicine systems. Because both systems were well documented, we concentrated on Ayurvedic and Chinese medicinal herbs. Dania Kowalska and Zhixiu Lin were the first graduate students to work on this project. We collected plant samples, synthesized herbal extracts, and devised a method to assess their ability to induce melanocyte (pigment cell) proliferation [1]. To repigment vitiligo patches, this characteristic would be required. We employed mouse melan-a cells that were produced in culture dishes. Professor Dorothy Bennett, a melanocyte biology expert at St. Georges Hospital in London, donated the cells, training, and a lot of extremely useful suggestions. One extract stood out among the over 30 herbs we examined! A black pepper water extract not only caused the pigment cells to grow quicker, but it also caused them to produce finger-like extensions called dendrites, which are vital for their role in the skin. A chemical called piperine, which is found in black pepper, had similar effects [2]. Piperine was referred to as a “oelead” molecule in the pharmaceutical industry, meaning it could be developed for use in treating diseases in its original or modified form.

Piperine’s Status as an oeLead Molecule

Pilot funds from the Vitiligo Society UK and the Institute of Chinese Medicine, UK helped us get started. We were able to purchase a multichannel micropipettor, a small but crucial piece of scientific equipment, thanks to a contribution of £250 from the Gulam K. Noon Foundation. Once we had our lead compound, however, I was able to secure significantly more finance (£200,000) from BTG plc, a UK technology transfer business. My study also put me in touch with the Vitiligo Society of the United Kingdom. I had the privilege of serving on the Society’s council and as secretary for several years. This invaluable experience allowed me to gain a better understanding of the issues and challenges that persons with vitiligo confront. 

We conducted additional investigations at King’s College London during the next three years (1997-2002), in which we created chemical variations (analogs) of piperine and assessed their capacity to induce melanocyte growth in culture dishes [3]. We examined piperine, THP, and RCHP for effects on skin pigmentation in mice because two analogs of piperine, abbreviated to THP and RCHP, showed very good efficacy. We were ecstatic to discover that all three chemicals were able to stimulate pigment cell proliferation in a specific strain of lightly pigmented mice, enabling their skin to darken visibly. When UV light was employed in addition to the chemicals, the impact was amplified [4]. Collaborations with Professor Robert Hider (a medicinal chemist) and Professor Antony Young (a photobiologist), as well as the devotion and hard effort of Radhakrishnan Venkatasamy (a PhD student) and Dr Laura Faas, were critical to this project (a postdoctoral fellow). These investigations enabled us to obtain worldwide patents for the treatment of vitiligo using piperine and its analogs.

Keeping the Vitiligo Fire Burning                                    

My personal life had taken an interesting turn at this point: I had married and relocated to the United States! In late 2002, I left King’s College London to work as a research faculty member in the Department of Neurology at Oregon Health & Science University (OHSU) in Portland, Oregon. Despite the fact that the focus of my research changed to herbs used in neurological illnesses, piperine and vitiligo were not ignored. Dr. Dennis Bourdette, Chair of the Department of Neurology, was enthusiastic about my pursuing this research, so I went out to find people at OHSU who could help bring the piperine study forward.

After demonstrating piperine’s efficacy in cells and mice skin in London, my next goal was to test it in humans. A medical school, research institutions, and, most crucially, a hospital are all part of OHSU. The Department of Dermatology has a strong research focus, so I approached Dr. Andrew Blauvelt, who works there, for assistance. This led to a meeting with dermatologists Dr. Eric Simpson and Dr. Ben Ehst, who assisted me in developing a thorough strategy (protocol) for a clinical trial of piperine in vitiligo patients. However, before embarking on a clinical trial, further information on piperine’s effects on human pigment cells, as opposed to mouse skin cells, was required. It was also crucial to look into piperine’s safety when applied to the skin. The effects of piperine on the development of melanoma are particularly important (a pigment cell cancer). Dr. Philippe Thuillier, an expert in skin cancer studies and Assistant Professor at OHSU’s Department of Public Health and Preventive Medicine, was fortunate enough to identify and recruit my help. Piperine does definitely accelerate the replication of human melanocytes in culture, including those from uninvolved skin of a vitiligo patient, according to our AdPharma, Inc.-funded research. Dr. Caroline lePoole of Loyola University in Chicago generously donated cell lines to our research. Piperine activated human melanocytes when they were created in a reconstructed skin model [5]. Professor Steven Jacques, Dr. Kevin Phillips, and Ravikant Samatham (Professor Steven Jacques, Dr. Kevin Phillips, and Ravikant Samatham) from OHSU’s Biomedical Engineering and Dermatology departments provided excellent support for this project, which used innovative optical methods to image pigmentation and melanocytes in skin models [6].

Piperine inhibits melanoma cell growth in cultured melanoma cells and stops melanoma cell growth in a rebuilt complete skin model, which is in agreement with other studies [5]. With the support of money I raised from OCTRI, we have introduced the HGF mouse model of melanoma (created by the National Cancer Institute) to OHSU to pursue this element of our study (the Oregon Clinical and Translational Research Institute). With pilot support from the Department of Dermatology’s Jesse Ettelson Fund for the Advancement of Dermatology Research, we are currently investigating the effects of piperine in this model. These current investigations are critical for determining piperine’s safety.

Heading for the Homestretch: Will Piperine work in humans?

Professor Sancy Leachman, a new Chair of Dermatology, was appointed in July 2013, giving this research a huge boost. Professor Leachman is a dermatologist who also works as a researcher. She is an expert in pigment cell biology and has a particular interest in pigment cell illnesses including vitiligo and melanoma, which is fortunate for this project! Professor Leachman is very excited about this initiative and has given her support and experience in the development of piperine as a new vitiligo treatment. She’s also brought on two more team members as an added benefit. Dr. Pamela Cassidy is the first, a medicinal chemist with knowledge in skin culture techniques, including the HGF mice model of melanoma discussed earlier. Eric Smith, a bright scientist with experience in the immunohistochemistry assessment of skin samples, is the second newcomer. Myself, Professor Leachman, Dr Cassidy, Dr Thuillier, and Eric Smith are part of a core group working to bring this discovery to the clinic.

My Personal and Professional Dedication to Finding a Cure

Piperine is on the verge of being tested in people thanks to a simple phone call from Maxine Whitton (who was recently granted an MBE for her services to vitiligo), a spark of a concept, and a considerable amount of devotion and effort on my part. It’s been a fantastic experience to apply my expertise of the drug development process to such a fascinating and potentially game-changing project. This would not have been feasible without the help of all of the wonderful collaborators, postdoctoral fellows, and students who have joined and supported my piperine and vitiligo vision, each with their own area of expertise. As previously stated, I am motivated by a personal desire to explore piperine as a vitiligo cure. After a visit in Central America in 2006, I had vitiligo as well. I’ve developed visible patches on my face, hands, and legs, and I’d like them to go gone! I consider myself fortunate that my research has resulted in new hope for a treatment for this challenging disease.

A competent team of researchers at OHSU — a world-renowned center with superior resources for clinical and basic scientific research — has dedicated themselves to the piperine project. 

Is Piperine Effective in the Treatment of Vitiligo? What you can do to assist.

If we can clarify how piperine works and demonstrate its safety and efficacy in a small â€oeproof of concept†human research, we’ll be able to convince a large pharmaceutical corporation to move forward with a vitiligo treatment very quickly. Unfortunately, funding for these investigations is lacking. We continue to explore traditional financing sources, but they are slow to respond and have limited resources. We are now looking out to the general public for funding, since we have a great team ready to start to work on this project. The money contributed will go toward our ongoing piperine research, both clinical and basic scientific. With the great prevalence of vitiligo around the world, little donations from those who are affected would quickly mount up and make a significant difference in our efforts. Make an online donation to our Vitiligo Research Fund to assist our piperine research for vitiligo.

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