Lifting the Next Generation of Natural Medicine Researchers

As long as humans have roamed the Earth, they have looked to the resources and life around them to heal their aches, pains and sicknesses. Even after thousands of years and great advances in technology, naturally occurring elements still play a vital role in our health and well-being.

For Dr. Angela Calderón, an associate professor in the Harrison College of Pharmacy’s Department of Drug Discovery and Development, a curiosity about natural products sparked as an undergraduate has turned into a career investigating how they can improve our health.

For her work, Calderón is the recipient of a pair of grants from the National Institutes of Health. A $148,960 R03 grant is supporting a project titled “Evaluation of the potential of ashwagandha extracts to produce CYP-mediated drug interactions,” while a $440,590 R15 grant is supporting “Unravelling the mechanism of acai BDS-anticancer drug interaction: A preliminary approach.” Both projects are funded by the National Center for Complementary and Integrative Health and the Office of Dietary Supplements.

“In the current times, our society is more curious about finding well-being using complementary and integrative medical approaches,” Calderón said. “Natural products of plant origin play a particularly important role. Over the years humankind has used plants for food and remedies for diseases, as plants are producers of biologically active natural products with diverse chemical structures. The chemical diversity found in compounds from plants offers opportunities for drug discovery of new bioactive molecules that can treat diseases.”

While the current grants allow Calderón to pursue her investigations of natural products, they also allow her to further another passion: mentoring the next generation of female scientists.

The R15 grant specifically is funded as part of the Research Enhancement Award Program for Health Professional Schools and Graduate Schools. In this program, Calderón is charged with exposing undergraduate and/or graduate students at health professional schools or graduate schools to meritorious research projects and strengthening the research environment of the institution.

“My R15 focuses particularly on training female and underrepresented minority students for biomedical sciences research careers,” Calderón said. “Students receive training in various disciplines such as pharmacognosy and natural products chemistry, pharmacology, pharmacokinetics and statistics.”

For Calderón, making mentorship part of her lab’s mission is also a matter of paying it forward. After studying her first medicinal plant during her undergraduate pharmacy studies, her research mentor sparked her curiosity in pharmacognosy and natural products chemistry research. Now, as a faculty member, she has her own program for undergraduate researchers in her lab.

“I strongly believe that providing research opportunities to diverse students can help diversify the workforce in STEM,” Calderón said. “I also strongly believe that diversity in science enhances creativity, and it can lead to unfettered discoveries and breakthrough innovations. I am an example of an individual belonging to those groups who received opportunities at the undergraduate, graduate and postdoctoral levels to build a research career in academia.”

Among those benefitting from the work in Calderón’s lab is Kabre Heck, a doctoral student from Hickory, North Carolina, pursuing the medicinal chemistry degree option. In 2022, Heck was selected by Auburn University’s Graduate School as one of the outstanding doctoral students.

“I knew I was interested in natural products and that I loved working with enzymes and chromatography, and when you add those things together, being in the Calderón lab just makes sense,” Heck said. “Dr. Calderón is a wonderful mentor who has helped me with challenges in research, academia and in life. She has pushed me to go after many opportunities that I would not have gone after without her support, and many of them have helped me tremendously in setting myself apart as a researcher and future job candidate.”

Another beneficiary of Calderon’s guidance is Zalaya Haynes, an undergraduate with a major in biomedical sciences and a minor in Africana studies who plans to apply to pharmacy school this year. Haynes is a recipient of the Auburn University Undergraduate Research Fellowship, under which Calderón is her mentor.

“For me, working under Dr. Calderón has been easy in the sense that she provides everything I need in order to understand the topics I am researching and get help if I need it,” Haynes said. “She is always looking for ways to help me advance by providing me opportunities that I may not have known about otherwise, and she always makes sure that we take care of ourselves and are not too overwhelmed while also holding us accountable for our projects and tasks we are doing.”

Undergraduate and graduate students like Heck and Haynes benefit from working in a lab that exposes them to NIH-funded projects like the two they are currently working on.

For the R03 project, Calderón and her team are studying the potential interactions between certain drugs and the common supplement ashwagandha. Specifically, they are investigating how Withania somnifera, commonly known as ashwagandha, interacts with certain liver enzymes and how these interactions can affect medications.

“My team is evaluating the potential of ashwagandha extracts to produce botanical-drug interactions,” she said. “In vitro experiments will be performed to determine if ashwagandha extracts inhibit or induce cytochrome P450 enzymes, the enzymes responsible for the hepatic metabolism of drugs. Inhibition or induction of liver enzymes is one mechanism by which some botanicals taken with other medicines may decrease the efficacy or increase toxicity.”

Naturally grown in India, the Middle East and Africa, ashwagandha is traditionally used as a rejuvenating herb. A popular botanical dietary supplement in the United States, it is being studied for its ability to improve resilience to neurological changes experienced in aging in the NIH-funded BENFRA Botanical Dietary Supplements Research Center. Researchers at the BENFRA Center at Oregon Health and Science University and Oregon State University are collaborating with Dr. Calderón in the R03 project.

“Early aging research shows that taking ashwagandha root extract helps to improve well-being, sleep quality and mental alertness by minor to moderate amounts in people aged 65-80 years,” Calderón said. “Some stress research shows that taking standardized ashwagandha root extracts 240 mg or 300 mg twice daily after food appears to improve symptoms of stress.”

For many people in older populations, the use of multiple drugs or medications is common for their chronic conditions. With so many potential botanical drug interactions, a primary outcome of the study is identifying safe uses of ashwagandha-containing dietary supplements.

For the R15 project, the team is investigating interactions between the supplement açaí and anticancer drugs.

Açaí is one of the top 40 botanical supplements in the United States market, but little is known about the combined use of the dietary supplement with anticancer drugs and the potential for adverse effects. Calderón’s team is working to establish a foundation of information on the interactions between açaí botanical dietary supplements and anticancer drugs. Her findings will be used to promote appropriate use of botanical dietary supplements and to improve understanding of potential adverse events.

Numerous claims about açaí’s potential to complement conventional chemotherapeutic drugs have been made,” Calderón said. “Açaí’s chemoprotective activity against cancer has been attributed to its anti-inflammatory, antioxidant, antiproliferative and proapoptotic properties in preclinical models.”