Biological Activity of 6,7-Dehydroxyroyleanone and Derivatives Obtained from Plectranthus aliciae (Codd) A.J.Paton.

The Plectranthus genus (Lamiaceae) is known to be rich in abietane diterpenes. The bioactive 6,7-dehydroxyroyleanone (DHR, 1) was previously isolated from Plectranthus madagascariensis var. madagascariensis and var. aliciae. This study aimed to explore the occurrence of DHR, 1, in P. aliciae and the potential bioactivities of new semisynthetic derivatives from DHR, 1. Several extraction methods were evaluated, and the hydrodistillation, using a Clevenger apparatus, afforded the highest yield (77.8 mg/g of 1 in the essential oil). Three new acyl derivatives (2-4) were successfully prepared from 1 (yields of 86-95%). Compounds 1-4 showed antioxidant activity, antibacterial effects, potent cytotoxic activity against several cell lines, and enhanced anti-inflammatory activity that surpassed dexamethasone (positive control). These findings encourage further exploration of derivatives 2-4 for potential mechanisms of antitumoral, antioxidant, and anti-inflammatory capabilities, studying both safety and efficacy.

Dehydroroyleanone as a Building Block for a Drug Delivery Platform Based on Self-Assembled Nanoparticles: Structural Studies and Chemical Modification.

6,7-Dehydroroyleanone (DHR) is a caspase-induced cytotoxic abietane diterpene, frequently found on Plectranthus spp. A pharmaceutical formulation consisting of a DHR-squalene conjugate was synthesized and analyzed by different techniques such as scanning electron microscopy (SEM). The facile production of the dispersion of DHR-squalene conjugate nanoparticles in phosphate buffer (pH 7.4) suggests that this nanodelivery platform may be an effective system to improve the solubility and bioavailability of DHR, so that therapeutical systemic levels may be achieved.

C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.

In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.

Family medicine physicians' perception and attitudes of herbal substances use in greater Lisbon region.

BACKGROUND: Previous works showed patients preference for herbal substances (HS) although they also highlighted a discrepancy with physicians' adherence to HS and its recommendation. HYPOTHESIS/PURPOSE: This study aimed to assess physician's perception and attitudes concerning the use of HS for their patients in a Family Medicine approach. STUDY DESIGN: Observational cross-sectional exploratory study. METHODS: A questionnaire survey was applied to National Health System physicians; 113 questionnaires were distributed in the Greater Lisbon region. RESULTS: 80 valid questionnaires were received. The age of participants ranges from 29 to 64 with mean age of M ±â€¯SD:51.9 ±â€¯10.0 years, mostly women (71.4%). Of these, 61.5% were unaware of traditional herbal medicinal products' (THMP) legal recognition and 67.3% of the difference between THMP and well-established use medicines. Absence of accordance between use and knowledge of herbal medicines (HM)/herbal products (HP) (p = 0.025) can be related to lack of Phytotherapy knowledge perception based on the nonexistence of specific training reported by 94.0% of physicians. Through factor analysis, three dimensions were obtained: Factor1, ``Use''; Factor2, ``Autonomy''; Factor3 ``Effort''. The overall Cronbach's α was 0.77, and 0.82 for Factor1. The evidence of use/prescription, has a correlation with ``Use'' (p < 0.0001), willingness to prescribe (p < 0.0001) and self-medication (p < 0.0001). There is a correlation (r = 0.605, p < 0.0001) between HS recommendation and self-medication. There were differences in use, perception and attitudes among Personalized-Health-Care Units and Family-Health Units physicians in relation to Factor1: p = 0.007 and Factor2: p = 0.021, age (p = 0.001), years of Medical career (p = 0.002), HM use (p = 0.014) and information about alternatives (p = 0.03). Physicians who answered correctly to the question on silymarin had higher scores in factor1 than those who did not: 1.76 vs. 1.25 (p = 0.019). CONCLUSION: Low adherence to HS and little use of HM/HP were confirmed, highlighting the need for specific knowledge in Phytotherapy and its regulatory framework. This knowledge will enable the evaluation of herb-drug interactions and HM/HP adverse effects by the physicians thus justifying the integration of programmatic contents about HS in Medical Education.

Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.

AIM: 6,7-dehydroroyleanone (DHR) is a cytotoxic abietane present in the essential oil of Plectranthus madagascariensis. METHODS/RESULTS: Different extraction parameters were tested, and its extraction optimization was accomplished with a Clevenger apparatus-based hydrodistillation. After isolation, its effect on microtubules, P-glycoprotein and caspases was assessed on several cell lines and the compound was coupled with hybrid nanoparticles. The results show that DHR does not interfere with microtubule formation, but evades the resistance mechanisms of P-glycoprotein. Strong activation of caspases-3 and -9 indicates that DHR is able to induce apoptosis by triggering the intrinsic cell death pathway. Moreover, the assembly of DHR with hybrid nanoparticles was able to potentiate the effect of DHR in cancer cells. CONCLUSION: DHR seems to be a promising starting material with anticancer properties to further be explored.

Anticancer Hybrid Combinations: Mechanisms of Action, Implications and Future Perspectives.

The exponential growth of cancer cases worldwide together with recent advances concerning the pathophysiological mechanisms of the disease at the molecular level led to a paradigm shift in chemotherapy, from monotherapy to targeted drug combination regimens. However, adverse effects and the emergence of multidrug resistance (MDR) limit the effectiveness of these therapies. In this context, hybrid combinations mixing anticancer drugs and bioactive phytochemical components from medicinal plants, or even plant extracts, that can act synergistically on multiple targets and signaling pathways represent a promising approach with the potential to expand the current therapeutic arsenal. This review aims to provide a synopsis on anticancer hybrid combinations based on their multi-target mechanisms and synergistic effects from an extensive literature search focusing mainly on publications from the last ten years. In most of these combinations, the phytochemical component was shown to enhance the anticancer activity of the chemotherapeutic agent and to sensitize chemoresistant tumors in several types of cancer. Hybrid combinations, due to synergistic interactions, are also associated with less severe adverse events since lower doses can be used to achieve the same therapeutic effect. Further preclinical and clinical studies are needed, as well as the development of an adequate regulatory framework, before hybrid combination therapy can be translated into clinical practice.