Cancer patients' behaviors and attitudes toward natural health products.

BACKGROUND: Natural health products (NHPs), including vitamins, minerals, and herbal supplements, are the most common complementary and alternative medicine (CAM) among cancer patients. Our survey determined the attitudes and behaviors of cancer patients toward natural complementary therapies that should be considered to implement an integrative approach in the future. METHODS: Our survey was conducted in four hospitals in Belgium. Questionnaires were posted online from October 2020 to October 2021 for cancer patients. Descriptive statistics were used to analyze the data. A [Formula: see text] test was applied to study the type of NHP consumed according to diagnosis time. Fischer's exact test compared patients who had changed their consumption since diagnosis and those who had not. RESULTS: Out of 349 questionnaires collected, only 59 met all inclusion criteria. 83.1 % of the patients agreed that conventional medicine (CM) could benefit from complementary therapies, but they did not estimate (72.3 % of the patients) that those latter are more effective than conventional medicine. More than half of the patients used five or more NHPs. The most frequent NHPs consumed daily were vitamins (64.4 %), followed by other products (i.e., probiotics, gemmotherapy, birch sap and omega 3/6) (42.4 %) and herbs (40.7 %). Almost all patients started taking NHPs before their cancer diagnosis, but 72.7 % have changed their consumption significantly (p = 0.009) since their diagnosis. Boosting the immune system (79.7 %) and limiting conventional treatment side effects (76.9 %) were the most common reasons for NHPs' use. 74.4 % of the patients did not take complementary therapies to delay or avoid conventional treatment. CONCLUSIONS: The combination and high diversity of NHPs consumption highlight the importance of educating patients and healthcare providers (HCPs) about the risk of drug interactions associated with these natural products. Most cancer patients are more interested in using this non-mainstream medicine to complement their conventional treatment than as an alternative. Knowing the patients' reasons and understanding patients' attitudes toward NHPs will be essential for HCPs to address NHPs' use.

Optimization of Long-Acting Bronchodilator Dose Ratios Using Isolated Guinea Pig Tracheal Rings for Synergistic Combination Therapy in Asthma and COPD.

The co-administration of a long-acting ß2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), has been shown to be beneficial in the management of non-communicable chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). The resulting relaxation of the airways can be synergistically enhanced, reducing symptoms and optimizing lung function. This provides an insight into more effective treatments. In this study, the LABAs formoterol fumarate dihydrate (FOR) and indacaterol maleate (IND) were each associated with tiotropium bromide monohydrate (TIO) to assess their synergistic potential. This was done using an appropriate ex vivo model of isolated perfused guinea pig tracheal rings, and pharmacological models of drug interaction. Among the dose ratios studied for both types of combination, a higher synergistic potential was highlighted for FOR/TIO 2:1 (w/w). This was done through three steps by using multiple additions of drugs to the organ baths based on a non-constant dose ratio and then on a constant dose ratio, and by a single addition to the organ baths of specific amounts of drugs. In this way, the synergistic improvement of the relaxant effect on the airways was confirmed, providing a basis for improving therapeutic approaches in asthma and COPD. The synergy found at this dose ratio should now be confirmed on a preclinical model of asthma and COPD by assessing lung function.

Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database.

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care.

Untargeted metabolomics approach to discriminate mistletoe commercial products.

Mistletoe (Viscum album L.) is used in German-speaking European countries in the field of integrative oncology linking conventional and complementary medicine therapies to improve quality of life. Various companies sell extracts, fermented or not, for injection by subcutaneous or intra-tumoral route with a regulatory status of anthroposophic medicinal products (European Medicinal Agency (EMA) assessment status). These companies as well as anthroposophical physicians argue that complex matrices composed of many molecules in mixture are necessary for activity and that the host tree of the mistletoe parasitic plant is the main determining factor for this matrix composition. The critical point is that parenteral devices of European mistletoe extracts do not have a standard chemical composition regulated by EMA quality guidelines, because they are not drugs, regulatory speaking. However, the mechanism of mistletoe's anticancer activity and its effectiveness in treating and supporting cancer patients are not fully understood. Because of this lack of transparency and knowledge regarding the matrix chemical composition, we undertook an untargeted metabolomics study of several mistletoe extracts to explore and compare their fingerprints by LC-(HR)MS(/MS) and 1H-NMR. Unexpectedly, we showed that the composition was primarily driven by the manufacturer/preparation method rather than the different host trees. This differential composition may cause differences in immunostimulating and anti-cancer activities of the different commercially available mistletoe extracts as illustrated by structure-activity relationships based on LC-MS/MS and 1H-NMR identifications completed by docking experiments. In conclusion, in order to move towards an evidence-based medicine use of mistletoe, it is a priority to bring rigor and quality, chemically speaking.

Vasorelaxant and antihypertensive effects of methanolic extracts from Hymenocardia acida Tul.

ETHNOPHARMACOLOGICAL RELEVANCE: In Congolese traditional medicine, decoctions of Hymenocardia acida root bark (HaRB) and trunk bark (HaTrB) are used for the treatment of conditions assumed to be hypertension. In this work, we propose to study the vasorelaxant effect of HaRB and HaTrB methanolic extracts on isolated rat thoracic aorta, to characterize the group of molecules responsible for the observed vasorelaxant activity, to evaluate the in vitro antioxidant activity of these extracts and to determine the antihypertensive activity of the HaRB extract on spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: The vasorelaxant effect of the HaRB and HaTrB methanolic extracts was studied on endothelium-intact aortic rings pre-contracted with phenylephrine (PE, 1µM). The mechanism of this vasorelaxant effect was investigated on endothelium-denuded vessels and on endothelium-intact aortic rings in the presence of three inhibitors: l-N(G)-nitroarginine methyl ester (100µM), indomethacin (10µM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10µM). To determine the nature of the compounds responsible for the vasorelaxant activity, we carried out a fractionation of the extracts and a thiolysis of the most active fraction followed by a liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) analysis. The extracts antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetric assay. In vivo anti-hypertensive activity of the HaRB extract was conducted on SHR. RESULTS: HaRB and HaTrB methanolic extracts produced a concentration-dependent vasorelaxation on intact aortic rings pre-contracted with PE (1µM). The vasorelaxant responses obtained were 95.3±1.5% (5µg/ml) and 100.6±3.0% (1µg/ml), respectively. The effect was markedly attenuated by removal of endothelium or pretreatment of aortic rings with all inhibitors except indomethacin. The LC/ESI-MS analysis of the thiolysis products indicated that the fraction which caused the most important vasorelaxation (97.9±2.5% at 3µg/ml) was a mixture of procyanidins and prodelphinidins, with a predominance of procyanidins. Both extracts and all fractions from HaRB extract showed a DPPH scavenging activity, ranging from 0.4 to 0.8 quercetin-equivalents. The HaRB methanolic extract reduced the systolic blood pressure in SHR (from 214±3mmHg to 194±4mmHg) after a 5-week treatment. CONCLUSIONS: The methanolic extracts of Hymenocardia acida root and trunk bark have vasorelaxant activity. The vasorelaxant effect observed is endothelium-dependent and seems mainly mediated through the NO-cGMP pathway. The COX pathway is not involved. The vasorelaxant activity appears to be due to polymeric procyanidins and prodelphinidins. These extracts also have an antioxidant effect. The extract of Hymenocardia acida root bark shows a significant but weak antihypertensive activity in SHR.

L-NAME iontophoresis: a tool to assess NO-mediated vasoreactivity during thermal hyperemic vasodilation in humans.

BACKGROUND: Decreased endothelial Nitric oxide (NO) bioavailability is one of the earliest events of endothelial dysfunction. Assessment of microvascular blood flow using a Laser Doppler Imager during local noninvasive administration of L-N-Arginine-Methyl-Ester (L-NAME) by skin iontophoresis may help discriminate the relative contributions of NO and non-NO pathways during a skin thermal hyperemic test. METHODS: In healthy nonsmokers, the effects of thermal vasodilation and sodium nitroprusside-mediated vasodilation were tested on skin pretreated with 0.9% saline solution, 2% L-NAME iontophoresis (n = 12), or intradermal injection of 25 nmol L-NAME (n = 10). The effects of L-NAME iontophoresis were also measured in a group of smokers (n = 10). RESULTS: L-NAME iontophoresis and intradermal injection of L-NAME decreased the skin response to local heating to a similar degree (-41% ± 4% vs. -44% ± 6%). L-NAME iontophoresis site-to-site and day-to-day coefficients of correlation were 0.83 and 0.76, respectively (P < 0.01). The site-to-site and day-to-day coefficients of correlation of L-NAME injection were lower than those of iontophoresis at 0.66 (P < 0.05) and 0.12, respectively (P = not significant). Sodium nitroprusside-induced skin hyperemia was not affected by L-NAME administration. L-NAME iontophoresis-mediated inhibition of skin thermal hyperemia was greater in smokers than in nonsmokers (P < 0.05). CONCLUSIONS: Laser Doppler Imager assessment of skin thermal hyperemia after L-NAME iontophoresis provides a reproducible and selective bedside method of qualitatively analyzing the contribution of the NO pathway to microvascular vasomotor function.

Vascular effects and antioxidant activity of two Combretum species from Democratic Republic of Congo.

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum racemosum P. Beauv (Combretaceae) leaves (CrLv) and root bark (CrRB) and Combretum celastroides subsp. laxiflorum Welw (Combretaceae) leaves (ClLv) are used in Congolese traditional medicine for several therapeutic purposes, notably for the treatment of conditions consistent with hypertension. The present study aims to investigate the vasorelaxant and in vitro antioxidant activities of these plants polar extracts and to examine the in vivo antihypertensive effect of the extract which displays the most potent vasorelaxant effect. MATERIAL AND METHODS: The vasorelaxant effect of CrLv, CrRB and ClLv methanolic extracts was studied on rat aorta rings pre-contracted with phenylephrine (PE, 1 µM) in the presence or absence of the endothelium. In some experiments, prior to the addition of the extract, rings were incubated for 30 min with either L-N(G)-nitroarginine methyl ester (L-NAME; 100 µM), a nitric oxide synthase (NOS) inhibitor, indomethacin (10 µM), a cyclooxygenase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 µM), a guanylate cyclase inhibitor. The antioxidant activity was determined by the measurement of the scavenging ability of extracts towards the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Blood pressure was measured on normotensive Wistar rats and spontaneously hypertensive rats (SHR) treated orally with a daily dose (40 mg/kg) of the CILv extract for 5 weeks. Tested extracts have been characterised by TLC profiles targeted at flavonoids. RESULTS: All tested extracts showed an important DPPH scavenging activity, ranging from 0.6 to 1.1 quercetin-equivalents. They caused a concentration-dependent vasorelaxation on intact aortic rings pre-contracted with PE (1 µM). The responses to CrRB and CrLv methanolic extracts reached 74.0±5.1% and 62.2±8.6% at a cumulative concentration of 50 µg/ml, respectively. The ClLv (10 µg/ml) extract was more active and, in the same conditions, relaxed aortic rings by 90.3±5.8%. The vasorelaxant activity of all extracts disappeared or was significantly attenuated by removal of the endothelium or after pretreatment with L-NAME or ODQ. Indomethacin only inhibited the activity of CrLv and CrRB extracts. The ClLv extract was able to lower the systolic blood pressure in SHR rats by 7% after a 5-week treatment. CONCLUSIONS: The present study shows that methanolic extracts from ClLv, CrRB and CrLv have an antioxidant activity and an endothelium-dependent vasorelaxant effect. ClLv induces the vasorelaxant effect through the NO-cGMP pathway while CrLv and CrRB extracts also act via a prostanoid pathway. ClLv extract demonstrated a modest but significant antihypertensive activity in SHR rats.