Botanical Medicine in Dermatology: Safety, Availability, and Evidence

The history of botanical medicine dates back to hundreds of thousands of years ago. The many beneficial properties of plants have recently been incorporated into pharmaceuticals. Reviewing the pathophysiology of certain skin diseases such as acne, we can understand how herbal medicine may be a beneficial adjunctive treatment. Specifically, pomegranate juice has the potential to attenuate oxidative stress by enhancing antioxidant response. However, in order to recommend botanicals as part of a comprehensive treatment plan, we must understand the safety, availability, and evidence for their use.


    • There are 3 tenants of botanical medicine to aid in proper use: safety, evidence, accessibility
    • There is new evidence of oxidative pathways contributing to the pathophysiology of acne
    • Pomegranate is an acne superfood

Botanical, or herbal, medicine has been used throughout the ages, dating back thousands of years with use in Traditional Chinese Medicine (TCM) and Ayurvedic medicine in India. Use of herbal medicine also dates back to Hippocrates’ legacy in North America and Europe.

Using herbs is not a new idea. Pharmaceutical use of herbs, however, is a novel practice. 200 years ago, the first pharmacologically active pure compound was produced from opium. Only 92 years ago was penicillin first discovered.

Many pharmaceuticals come from botanicals. Out of 177 drugs approved for cancer treatment, 70% are based on natural products. Similarly, out of 252 drugs in the World Health Organization’s (WHO) essential medicine list, 11% are exclusively of plant origin.

It is rare to find research on botanicals for specific dermatologic conditions. Most research is conducted in China. Why is there little botanical research in the states? Well, conducting research is expensive, and companies that fund research cannot patent herbs. Plants have many compounds that work synergistically to have an effect. Most research is conducted on a focused target. Conducting research on a collective system is difficult.

As a Western society, why would we consider using botanicals? First, many conventional treatments are not working and it behooves us to expand our toolbox. Patient preference is another reason. Patients are asking for herbal supplements and the supplement market is forecasted to reach 62 billion dollars by 2025. With 85,000 supplements for sale in the United States, how can patients safely choose which supplement is best? Patients need guidance from clinicians to prevent harm; prevent herb-herb interaction or herb-drug interactions.

This leads us to 3 important criteria for using botanicals:

    1. Safety
    2. Evidence
    3. Accessibility

There are several things to consider in terms of safety:

    • What part of the botanical is being used? Root, seed, leaves, fruit?
    • Is it an oral or topical formulation?
    • What dose should be used and for how long?
    • Are there any herb-herb or herb-drug interactions to be aware of?
    • What population can the herb be used in safely? Children, pregnant women, certain diseases, illness or conditions. For example, licorice can increase blood pressure and should be avoided in patients with hypertension.

There are several sources to assess botanical safety:

    • Natural medicines database
    • Pubmed research
    • UpToDate drug interactions checker
    • Botanical experts: naturopathic doctors, TCM practitioners, Ayurvedic practitioners, Registered herbalists

What evidence is there to support use of herbal medicine? Natural medicines database and Pubmed research contribute to evidence-based research of botanicals. However, herbs have been used for hundreds to thousands of years and clinical experience is the mainstay for clinical indication. An integrative approach to skin disease with botanical experts can augment disease-specific treatments.

Finally, in terms of accessibility, we strive for herbs that are abundant and easily found with beneficial properties for use. And, we need cost-effective botanicals.

Let’s transition to the use of botanicals in skin disease. Acne is a common skin condition in Western, industrialized societies. The pathophysiology of acne involves abnormal keratinization, excess sebum production, inflammation, and bacterial overgrowth of Propionibacterium acnes. Studies of indigenous populations do not show evidence of acne or acne-like lesions in the entire population. However, when indigenous people move to Western societies, they develop acne.

What is causing these abnormal processes in the skin and hair follicles leading to acne? Acne is closely related to the Western diet: high glycemic index foods, dairy products, and saturated fats. Diet-induced insulin-like growth factor (IGF-1)-signaling leads to aberrant sebaceous gland homeostasis.

Research has shown that the mTOR pathway, a central regulator of mammalian metabolism and physiology, is involved in the pathogenesis of acne. FoxO1 is a metabolic transcription factor that inhibits the mTOR pathway.

FoxO1 also functions to:

    • Inhibit IGF1-signaling
    • Inhibit lipogenesis
    • Suppress androgen signaling
    • Reduce oxidative stress
    • Control antimicrobial peptide synthesis

Therefore, it is hypothesized that acne may be due to a relative deficiency of FoxO1 within the nucleus of sebocytes. When FoxO1 is inhibited, P. acnes can overgrow and cause a positive feedback loop that further inhibits FoxO1.

There is a lot of research demonstrating the benefits of pharmaceuticals used in acne on FoxO1 function:

    • Isotretinoin – upregulation of FoxO1 expression
    • Benzoyl peroxide – increase nuclear levels
    • Tetracyclines – facilitation of FoxO1 export from the nucleus
    • Azelaic acid – upregulation of FoxO1 expression

Next, let’s look at how pomegranate affects the mTOR pathway.  Banerjee, N, et al. performed a study in rats with azomethane-induced colorectal foci. Animals were randomly distributed by weight into control juice and pomegranate juice groups. In this study, it was found that rats that consumed pomegranate juice had decreased expression of IGF, pPI3K/AKT, and mTOR. Therefore, the anti-inflammatory effects of polyphenols from pomegranate are mediated through the suppression of the mTOR pathway.

Further studies have shown that two polyphenols, in particular, luteolin and apigenin, contribute to rapid nuclear translocation of FoxO1 in a dose-dependent fashion. Luteolin is a main component of pomegranate fruit and peel, further contributing to the beneficial effects of this botanical as an adjunctive treatment of acne.

Malondialdehyde (MDA) is one of the final products of lipid peroxidation and is used as a marker of oxidative stress. Human studies have shown significantly elevated levels of MDA in patients with severe acne.

Ammar, A, et al. tested the hypothesis that pomegranate juice supplementation would decrease acute and delayed oxidative stress responses after a weightlifting training session. Nine elite weightlifters performed two Olympic-Weightlifting sessions after ingesting either the placebo or pomegranate juice supplements. Venous blood samples were collected at rest, 3 minutes, and 48 hours after each session. Compared to the placebo condition, pomegranate juice supplementation attenuated the increase in malondialdehyde. It was also found that during the 48-hour recovery period, pomegranate juice supplementation accelerated the recovery kinetics of enzymatic antioxidant defenses such as those of MDA.

If we revisit our tenants of botanical use, we can conclude that pomegranate has convincing evidence for adjunctive use in skin conditions such as acne. Both pomegranate fruit and juice are relatively affordable and easy to find. When it comes to safety, pomegranate shows no interactions with systemic acne medications such as isotretinoin or doxycycline.

Let’s review some key takeaways:

    • Assess the possibility of using a botanical-based on 3 criteria: safety, evidence, and accessibility
    • Work together with other (integrative) professionals to round out gaps in your botanical knowledge base
    • Consider using pomegranate as part of an acne treatment protocol as there is supportive evidence for its oxidative benefits

The above article was written by Dr. Mojgan Hosseinipour and represents her interpretation of the information presented by Julie Greenberg, ND during her lecture “ Using Botanical Medicine in Dermatology ” at the 2020 Integrative Dermatology Symposium.

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