by Christos Ganos

Cretan rock rose or Cistus creticus L. (Cistaceae) is endemic to the Mediterranean region and especially to several islands of Greece. Today it has become, along with its hybrids, a popular garden plant in temperate Europe including Southern England. In fact, there are two freely-flowering plants of Cistus creticus, located by the west gate of Brunswick Square, close to Mecklenburgh Square Garden (Figure 1). Unyielding to the elements and requiring minimal watering and overall care, C. creticus stands as an attractive ornamental plant choice even for the least experienced plant enthusiast. Cistus has a rich history of traditional use for its medicinal and cosmetic attributes and is currently popular in Europe, amongst best-selling infusions with antioxidant, anti-inflammatory and potential antibacterial and antiviral effects.

Introduction

As the name suggests, plants of the Rock Rose family are very hardy and grow on rocky surfaces and unfertile ground. They are uniquely adapted to the barren land and unforgiving weather of the Mediterranean (Thanos et al. 1992) by reducing the size of their leaves fivefold during summer in order to preserve water (Aronne et al. 2001). Additionally, Cistus plants’ seeds are very resilient and are able to sprout during intense heat or even after a destructive forest fire, giving them an ecological edge (Ferrandis et al., 1999). Rock roses are generally short woody bush plants which can reach up to one meter in height and develop beautiful pink/purple or white flowers. Tiny hairs cover their green parts, which can excrete a resin responsible for their characteristic pleasant rosy aroma. C. creticus is a representative member of its family and genus, exhibiting all above mentioned characteristics (Kavvadas 1990, Gülz et al. 1996). It has many subspecies and hybrids, found all across the reaches of the Mediterranean Sea but the best documented one, namely Cistus creticus subsp. creticus, is found mainly on the shores of the Greek island of Crete (Kavvadas 1990, Demetzos et al. 2002)

A Unique Resin

C. creticus excretes a dark brown, resinous aromatic material called “Ladanon” (Maggi et al. 2016), which is highly sought after for the production of aromas as well as therapeutic preparations. It is traditionally harvested during midday in hot summer days, at which time it melts into a viscous semiliquid. The harvesting technique remains almost unchanged over the centuries, being carried out with a form of rake that has pieces of leather attached to it, on which the resin adheres (Figure 2).

History: from ancient paintings to your local pharmacy

The first documented reference to this small plant comes from the Pharaoh era in Egypt. According to the Ebers papyrus, which is considered the oldest surviving pharmaceutical text dating back to 1550 B.C.E., Egyptians were using resin from the plant as an aphrodisiac balsam (Nicoletti et al. 2015), anti-cholera medicine and for mummy embalming.

The plant saw extensive use in Minoan Crete society (considered to be the first European Civilization: 2700-1450 B.C.E.). and is even represented on Minoan paintings (Figure 3). Herodotus (484-425 B.C.E.), known as “the father of history” mentions in his book “The Histories” how the Arabs obtained the aromatic “Ladanon resin” from the beard of goats that grazed on the plant (Figure 4). Later, Hippocrates (460-377 B.C.E.) named the plant “Cistus (from the Greek: Κίστος) and praised its valuable resin. In the Roman era, the physician Celsus (25-50 C.E.) describes the use of “Ladanon” in plasters for the treatment of malignant sarcoma. Furthermore, Dioscorides (10-90 C.E.) mentions in his pharmaceutical encyclopaedia (Pharmacopoeia) called “De Materia Medica” that the plant had been used for over 2000 years until his era. Other reports claim that “Ladanon” was made into a paste to treat the distressing condition of…hair loss, for the Roman Emperor Julian.

In north western Europe Cistus is mentioned for the first time in botanical books of the Middle Ages as an aromatic agent (Deforce 2006) (Figure 5). Overall, the plant has been used traditionally by many nations as an antimicrobial, antifungal, expectorant and for its anti-inflammatory effects such as the treatment of stomach ulcers and kidney inflammations (Ahmad et al. 1993, Attaguile et al. 2004, Azevedo et al. 2015, Papaefthimiou et al. 2014, Rebaya et al. 2016, Kühn 2011). Nowadays the plant is still being traditionally used in Cretan villages as a herbal tea for combatting flu, cough, kidney stones and its resin is a component of the “holy anointing oil” (myrrh) used in ceremonies of the Greek Orthodox Church.

Medicinal preparations of Cistus, which are widely available in pharmacies today, still claim some of the abovementioned traditional medicinal effects. In fact, the European Medicines Agency has set Cistus on a priority list for assessment, which could potentially lead to its receiving Traditional Herbal Medicinal Product (THMP) status in the EU. Meanwhile in several European countries, there are over the counter products available containing rock-rose, with various therapeutic uses, under different regulatory status (food supplements, herbal medicines, cosmetics and medical devices).

A Plethora of Beneficial Chemical Constituents

Cistus creticus water extracts such as infusions and decoctions, contain multiple phenolic compounds especially flavonoids (such as compounds found in green tea). These compounds comprise of many hydroxyl (-OH) groups which bestow an antioxidant effect upon them, bringing forth various health benefits from their use (Kalus et al. 2009). The plant’s resin and aerial parts are rich in monoterpenes, small, volatile compounds responsible for “ladanon” resin’s rich aroma (Figure 6). These include pinene (pine trees’ aroma), the familiar camphor and carvacrol, the compound responsible for oregano’s pungent warm odour. They are used by plants to “lure” insects for pollination while they exhibit a broad range antimicrobial activity (Barrajón-Catalán et al. 2015). Additionally, the plant produces more complex sesquiterpenes and diterpenes which are like ‘’cousin compounds’’ to the monoterpenes. The abovementioned constituents are created by plants by plants as a chemical defence mechanism against herbivore organisms. Consequently, sesquiterpenes have antiparasitic, antimicrobial and anti-inflammatory effects while diterpenes apart from these effects are also adept at “killing” cells. Although, these… “cell killers” might sound dangerous, they do not target our healthy human cells but fixate on microbes, fungi and viruses while there have been even some reports of cancer preventative activity (Güvenç et al. 2005)

Is There Proof?

After shedding some light on the identity, story and inner world of Cistus creticus, we stumbled upon many potential “beneficial uses” for it. Therefore, the pressing question remains: is there scientific evidence to back the claims coming from traditional sources? In the next paragraphs this matter will be addressed by presenting scientific data available for each of the individual, alleged effects of Cistus while briefly describing the effects themselves.

Antioxidant Effects

Antioxidant activity has been linked with the alleviation of age-related health issues such as skin ageing, cancer and cardiovascular diseases. These ailments are often caused by the destructive effects of oxygen derivatives found in increasingly larger amounts in our body as it ages or when it is exposed to conditions such as UV radiation and air pollutants (oxidative stress). Plants are full of antioxidant compounds that eliminate these so-called free oxygen radicals since they are under constant oxidative stress from the sun’s radiation themselves. (Di Ferdinando et al. 2014, Martínez-Ferri 2000) C. creticus is no exception and its abundance in antioxidants was already stated. Studies carried out in vitro (in a laboratory environment) highlighted the plant’s phenolic compounds’ (extracted in water) ability to destroy model free oxygen radicals (Sayah et al. 2017, Akkol et al 2012, Attaguile et al. 2000) and were further backed by more sophisticated laboratory methods (LC-online TEAC) (Riehle 2013). Another study showed how aqueous extracts of Cistus can reduce free radical damage to DNA models, induced by UV light (Attaguile et al. 2004). Lastly, there are numerous studies on other plants containing these compounds, and on the compounds themselves, pointing towards their efficacy.

Antibacterial effects

Cistus plants have been used since antiquity for their therapeutic effects against microbial infections (Tomás-Menor et al. 2013) This fact triggered studies which support the antimicrobial effects of these plants both against multiple types of bacteria (Barrajón-Catalán et al. 2010, Bedoya et al. 2010, Tomás-Menor et al. 2013). According to scientific data, mouth washes with Cistus creticus infusions reduce bacterial content in the oral cavity and can even aid against tooth decay (Riehle et al. 2013, Wittpahl et al. 2015). Diterpenes of the plant have been proved to be the driving force behind the antimicrobial activity of such infusions (Rauwald et al. 2010). Finally, the phenolic compounds of Cistus plants are also seemingly responsible for a broad range antimicrobial activity, such as against certain Mycobacteria (Haouat et al. 2013). They also appear to have a positive synergetic effect with first line antibacterials. Ladanon has additionally been shown to have a potent in vitro antimicrobial profile (Chinou et al. 1994, Kalpoutzakis et al. 1998, Tomás-Menor et al. 2015).

Cytotoxic effects

It is worth noting a common misunderstanding frequently observed in mass media articles about medicine against cancer. If the evidence supporting the use of such a medicine is solely in vitro, it is called cytotoxic. If there is in vivo (animal experiments) supporting evidence, it is called antitumor. Only if there is clinical evidence (human trials) supporting its use can a medicine be called as anticancer.

Validity behind the traditional use of C. creticus against cancer cells was recently revealed while extracts rich in diterpenes showed promising in vitro efficacy against breast, melanoma and cervix cancer cell lines (Chinou et al. 1994, Kalpoutzakis et al. 1998, Dimas et al. 1998, Dimas et al. 2001, Skorić et al. 2012). Another study exhibited positive effects against human leukemic cells (Dimas et al. 1998). Nano-sized drug carriers have been proved to improve the anticarcinogenic effects of Cistus diterpenes and new in vivo (animal) studies are on the way using such carriers (Dimas et al. 1998, Matsingou et al. 2006). Furthermore, cytotoxic effects of water extracts have been evidenced in vitro, against lung, prostate, breast and intestinal cancer cells (Kalpoutzakis et al. 1998, Dimas et al. 2000, Matsingou et al. 2006, Vitali et al. 2011). Although the plant’s extracts demonstrated adequate cancer cell inhibition, healthy human cells were not affected in these studies, hinting at a good safety profile (Moreira et al. 2017). Overall, interest is gathering on this effect of Cistus but evidence is still severely lacking in order to make claims for such a severe condition as cancer.

Antiviral effects

Two case studies (Droebner et al. 2007, Ehrhardt et al. 2007) have described the antiviral effects of Cistus extracts against common cold while a clinical trial demonstrated their beneficial effects on oral and throat infections. The effectiveness of Cistus at reducing the duration and severity of symptoms versus placebo in patients with upper respiratory infections was evidenced in another double-blind clinical trial (Kalus et al. 2009). It is worth mentioning that Cistus extracts in the above trial were effective mainly when taken before the onset of infection, indicating towards a preventative action. In a study that highlighted strong antiviral activity of the plant’s extracts against HIV, some hints towards its possible mechanism of action were speculated (Rebensburg et al. 2016). After a series of experiments, researchers have established that C. creticus extracts target selectively the protective capsule surrounding the virus, inhibiting the entrance of viruses in human cells, a procedure necessary for them to exert their harmful effects. Therefore, the viral material does not manage to enter cells it remains inactive and harmless. However, Cistus extracts should be ingested before the virus manages to enter the cells for them to function effectively. Concluding, results of studies concerning Cistus creticus have indicated positive, broad spectrum antiviral effects while the selective targeting of viral capsules translates into low toxicity (unlike other plants’ extracts which harm human cells as well). However, this evidence is still on the infant stage, and more concrete clinical data is needed for any claims to be made.

Spasmolytic effects

The presence of constituents with potential relaxing effect on smooth muscles of the gastrointestinal tract seem to be in line with the traditional use of rock rose extracts for gastrointestinal disorders. Experimentally, the muscle relaxing effects of C. creticus water extracts were supported in animal trials (de Rojas et al. 1995, Attaguile et al. 2004). Additionally, evidence leads to the speculation that these effects are brought about by the extracts’ phenolic compounds and specifically flavonoids, since these compounds are known to cause muscle relaxation.

Toxicity

No data on the reproductive and developmental toxicity, genotoxicity and carcinogenicity of Cistus creticus are available in literature, therefore the use during pregnancy and lactation as well as in children and adolescents cannot be recommended. However, the limited existing clinical data, indicates that toxic effects for Cistus are rather low.

Conclusions

Overall, C. creticus is a unique, beautiful and interesting medicinal plant. Consumption of Cistus herbal tea remedies, used since ancient times and still produced today, can bring about multiple beneficial effects, as discussed above, supported by varying levels of available evidence. The most common and established such effects are the relief of cough related to common cold as well as, externally, the alleviation of skin irritations / inflammations. However, it should be noted that production of a quality Cistus herbal remedy, which is in fact a form of medicine, is neither an easy nor an inexpensive process. Specific steps, much like those followed for making conventional medicine, need to be followed on the agricultural and manufacturing level in order to ensure reproducible safety and efficacy. Additionally, in the case of herbal preparations, focus is also directed to the sustainable harvesting of plant material for the conservation of biodiversity. Therefore, C. creticus products of certified high quality, plausibility and safety should be preferred by potential consumers.

©Christos Ganos 2020. All rights reserved.

Christos Ganos is a pharmacist, plant enthusiast and MSc student in Medicinal Natural Products and Phytochemistry at the UCL School of Pharmacy, University College London, UK.
Christos can be contacted by sending a message from the contact form on this website.

Disclaimer

In this essay we do not to advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflets (i.e. for THR products)

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