Labdanum Resin from Cistus ladanifer L. as a Source of Compounds with Anti-Diabetic, Neuroprotective and Anti-Proliferative Activity.

Labdanum resin or "gum" can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of α-amylase and α-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher α-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg/mL, respectively). Zamorean absolute showed the highest α-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic/anti-proliferative activity at 24 h exposure (IC50 = 45-70 µg/mL, for Caco-2; IC50 = 60-80 µg/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 ≥ 200.00 µg/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.

Labdanum Resin from Cistus ladanifer L.: A Natural and Sustainable Ingredient for Skin Care Cosmetics with Relevant Cosmeceutical Bioactivities.

Labdanum resin from Cistus ladanifer L. (Cistaceae) is an abundant natural resource in the Iberian Peninsula worth being explored in a sustainable manner. It is already used in the cosmetic industry; mainly by the fragrances/perfumery sector. However, given the highest market share and traditional uses, labdanum resin also has the potential to be used and valued as a cosmetic ingredient for skincare. Aiming to evaluate this potential, labdanum methanolic absolute and fractions purified by column chromatography were characterized by UPLC-DAD-ESI-MS and then evaluated for UV-protection, antioxidant, anti-elastase, anti-inflammatory, and antimicrobial activities. Labdanum absolute represented ~70% of the resin; diterpenoid and flavonoid fractions represented ~75% and 15% of the absolute, respectively. Labdane-type diterpenoids and methylated flavonoids were the main compounds in labdanum absolute and in diterpenoid and flavonoid fractions, respectively. Labdanum absolute showed a spectrophotometric sun protection factor (SPF) near 5, which is mainly due to flavonoids, as the flavonoids' SPF was 13. Low antioxidant activity was observed, with ABTS radical scavenging being the most significant (0.142 ± 0.017, 0.379 ± 0.039 and 0.010 ± 0.003 mgTE/mgExt, for the absolute and flavonoid and terpene fractions, respectively). Anti-aging and anti-inflammatory activity are reported here for the first time, by the inhibition of elastase activity (22% and 13%, by absolute and flavonoid extract at 1 mg/mL), and by the inhibition of nitric oxide production in LPS-induced RAW 264.7 cells (84% to 98%, at 15 µg/mL extracts, flavonoid fraction the most active), respectively. Antimicrobial activity, against relevant skin and cosmetic product microorganisms, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Escherichia coli, revealed that only S. aureus was susceptible to labdanum absolute (MIC: 1.2 mg/mL) and its fractions (MIC: <0.3 mg/mL). In conclusion, labdanum resin showed potential to be used in sunscreen cosmetics, anti-inflammatory skincare cosmeceuticals or medicines but has low potential as a cosmetic product preservative given the low antioxidant and low-spectrum antimicrobial activities.