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.

Croton sublyratus (Euphorbiaceae) is a traditional medicinal plant used by the Thai populace to treat helminthic infections and dermatologic conditions. In present study, eight new labdane-type diterpenoids, crotonoids A-H (1-8) and one known analogue (9) were isolated from the aerial parts of C. sublyratus. Compounds 6 and 7 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compound 8 exhibited a rare 14,15,17-trinor-labdane skeleton. The structures of all these diterpenoids were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 9 exhibited moderate anti-inflammatory activity via the inhibition of NO production in lipopolysaccharide-induced RAW 264.7 cells.

Labdane-related diterpenoids (LRDs), a subgroup of terpenoids, exhibit structural diversity and significant commercial and pharmacological potential. LRDs share the characteristic decalin-labdanic core structure that derives from the cycloisomerization of geranylgeranyl diphosphate (GGPP). Labdanes derive their name from the oleoresin known as \'Labdanum\', \'Ladano\', or \'Aladano\', used since ancient Greek times. Acetylated labdanes, rarely identified in plants, are associated with enhanced biological activities. Chemical analysis of Cistus creticus subsp. creticus revealed labda-7,13(E)-dien-15-yl acetate and labda-7,13(E)-dien-15-ol as major constituents. In addition, novel labdanes such as cis-abienol, neoabienol, ent-copalol, and one as yet unidentified labdane-type diterpenoid were detected for the first time. These compounds exhibit developmental regulation, with higher accumulation observed in young leaves. Using RNA-sequencing (RNA-seq) analysis of young leaf trichomes, it was possible to identify, clone, and eventually functionally characterize labdane-type diterpenoid synthase (diTPS) genes, encoding proteins responsible for the production of labda-7,13(E)-dien-15-yl diphosphate (endo-7,13-CPP), labda-7,13(E)-dien-15-yl acetate, and labda-13(E)-ene-8α-ol-15-yl acetate. Moreover, the reconstitution of labda-7,13(E)-dien-15-yl acetate and labda-13(E)-ene-8α-ol-15-yl acetate production in yeast is presented. Finally, the accumulation of LRDs in different plant tissues showed a correlation with the expression profiles of the corresponding genes.

Chemical investigation of the roots of Euphorbia pekinensis Rupr. led to the isolation of five undescribed labdane diterpenoids \"(4S, 5S, 9R, 10S, 13R)-18-O-galloyl-labda-8(17), 14(15)-dien-13-ol; (4S, 5S, 9R, 10S, 13R)-13-hydroxy-labda-8(17), 14(15)-dien-18-one; (4S, 5S, 9R, 10S, 13R)-18-O-acetyl-labda-8(17), 14(15)-dien-13-ol; (4S, 5S, 9R, 10S)-labda-8(17), 13(16), 14(15)-trien-18-ol; (5R, 6R, 9R, 10S, 13R)-labda-8(17), 14(15)-dien-6,13-diol\", two undescribed pimarane diterpenoids \"(2R, 5S, 9R, 10S, 12R, 13R)-2,12-dihydroxy-isopimara-7,15-dien-3-one; (5S, 9R, 10S, 12R, 13R)-2, 12-dihydroxy-isopimara-1, 7, 15-trien-3-one)\", together with nine known diterpenoids, including three pimarane-type \"(3β,11α,13α)-3,11-dihydroxypimara-7,15-diene-2,12-dione; (11R, 12S)-2,11,12-trihydroxy-ent-isopimara-1,7,15-trien-3-one; isopimara-7,15-dien-3β-ol)\", five abietane-type \"helioscopinolide A-C; helioscopinolide E; helioscopinolide I″, and one lathyrane-type \"jolkinol B\". The structures of these compounds were elucidated by analysis of HRESIMS, 1D NMR, 2D NMR, and X-ray diffraction. These sixteen compounds were evaluated for cytotoxic activity in vitro against three human cancer cell lines, U-937, LOVO, and K-562. Jolkinol B exhibited IC50 of 3.60 μM and 8.44 μM against U-937 and LOVO cell lines, (4S, 5S, 9R, 10S, 13R)-18-O-galloyl-labda-8(17), 14(15)-dien-13-ol displayed IC50 of 5.92 μM against U-937 cell lines, isopimara-7,15-dien-3β-ol showed IC50 of 0.87 μM against K-562 cell lines.

Three labdane-type [multisins A-C (1-3)], two guaiane-type [multisins D (4) and E (5)], and one eudesmane-type [multisin F (6)] previously undescribed terpenoids, together with 14 mono- (7-20) and seven dimeric- (21-27) known terpenoids, were isolated from the 90% MeOH extract of the whole plant of Chloranthus multistachys. Their structures and absolute configurations were determined by extensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 are rare trinor-sesquiterpenes with a de-isopropyl guaiane skeleton, whereas compound 6 is a rearranged dinor-eudesmene featuring an uncommon octahydro-1H-indene ring system. Among the isolates, the dimeric lindenane sesquiterpenoid shizukaol C (25) exhibited the most potent (IC50 = 8.04 μM) anti-neuroinflammatory activity by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells.

Three new labdane-type diterpenoids, callicapene M3-M5 (1-3) were isolated from the Callicarpa macrophylla Vahl. Their structures were identified by spectroscopic method. The isolated compounds were evaluated for inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells by using MTT assays. Compounds 1-3 showed potent inhibitory activity, with IC50 value of 48.15, 46.31 and 38.72 μM respectively.