Luigi Gori

Herbal Medicine Today: Clinical and Research Issues

Herbal medicine is the use of medicinal plants for prevention and treatment of diseases: it ranges from traditional and popular medicines of every country to the use of standardized and tritated herbal extracts. Generally cultural rootedness enduring and widespread use in a Traditional Medical System may indicate safety, but not efficacy of treatments, especially in herbal medicine where tradition is almost completely based on remedies containing active principles at very low and ultra low concentrations, or relying on magical-energetic principles. In the age of globalization and of the so-called ‘plate world’, assessing the ‘transferability’ of treatments between different cultures is not a relevant goal for clinical research, while are the assessment of efficacy and safety that should be based on the regular patterns of mainstream clinical medicine. The other black box of herbal-based treatments is the lack of definite and complete information about the composition of extracts. Herbal derived remedies need a powerful and deep assessment of their pharmacological qualities and safety that actually can be realized by new biologic technologies like pharmacogenomic, metabolomic and microarray methology. Because of the large and growing use of natural derived substances in all over the world, it is not wise to rely also on the tradition or supposed millenarian beliefs; explanatory and pragmatic studies are useful and should be considered complementary in the acquisition of reliable data both for health caregiver and patients.

Ear acupuncture in European traditional medicine.

Auricular acupuncture is a diagnostic and treatment system based on normalizing the bodys dysfunction through stimulation of definite points on the ear. Rudimentary forms of acupuncture which probably arose during the Stone Age have survived in many parts of the world right down to present day. It was used in the ancient Egypt, Rome, Greece and all the Mediterranean area. It is a microacupuncture technique similar to reflexology, and was first described in France in 1950 by Paul Nogier who is considered the Father of modern ear acupuncture. It was speculated that the technique works because groups of pluripotent cells contain information from the whole organism and create regional organization centers representing different parts of the body. Nevertheless stimulation of a reflex point in the ear seems relieve symptoms of distant pathologies. Modern research is confirming the efficacy of ear acupuncture for analgesia and anxiety related disease, while tobacco dependence and other substance abuse still need confirmation. Actually main methodological problems with auricular acupuncture are that exist too many maps with little agreement regarding point location in the ear, and that the correspondence or reflex systems does not correlated with modern knowledge of anatomy and physiology.

Use, Attitudes and Knowledge of Complementary and Alternative Drugs (CADs) Among Pregnant Women: a Preliminary Survey in Tuscany.

To explore pregnant womens use, attitudes, knowledge and beliefs of complementary and alternative drugs (CADs) defined as products manufactured from herbs or with a natural origin. A preliminary survey was conducted among 172 pregnant women in their third trimester of pregnancy, consecutively recruited in two obstetrical settings; 15 women were randomly selected to compute a test-to-retest analysis. Response rate was 87.2%. Test-to-retest analysis showed a questionnaires reproducibility exceeding a K-value of 0.7 for all items. Mean age was 32.4 ± 0.4 years; most women were nulliparae (62.7%). The majority of subjects (68%) declared to have used one or more CADs during their lifetime; 48% of pregnant women reported taking at least one CAD previously and during the current pregnancy. Womens habitual use of CADs meant they were at higher risk of taking CADs also during pregnancy (adjusted odds ratio = 10.8; 95% confidence interval: 4.7–25.0). Moreover, 59.1% of the subjects were unable to correctly identify the type of CADs they were using. The majority of women resorted to gynecologists as the primary information source for CADs during pregnancy, while they mainly referred to herbalists when not pregnant. Habitual use of CADs seems to be a strong predictor for their ingestion also during pregnancy; in addition most subjects were unable to correctly identify the products they were taking. In the light of the scanty data concerning the safety of CADs during pregnancy, these preliminary results confirm the need to investigate thoroughly the situation of pregnant women and CADs consumption.

Myopathies associated with red yeast rice and liquorice: spontaneous reports from the Italian Surveillance System of Natural Health Products

Many drugs can be responsible for muscle injuries. Besides statins, recognised as the drugs most commonly associated with severe myopathies, other medications such as neuroleptics, proton pump inhibitors and recently gabapentin [1] have been associated with this type of adverse drug reaction (ADR). Recent case reports have highlighted that active compounds from medicinal plants can also be responsible for myopathies [2, 3], including rhabdomyolysis but a systematic evaluation of reporting databases is still lacking. In the present study, the Italian ADR database [4, 5] of natural health products was analyzed with the aim of evaluating the possible ‘signal alarms’ due to herbal medicines and muscle injuries. A panel of experts, including a medical toxicologist, a pharmacist and a physician expert in herbal medicine reviewed all reports of myopathy to define the causality assessment using the Naranjo probability scale [6]. From April 2002 to December 2007, nine reports of muscle disorders were identified, of which seven were reported by phytotherapy specialists, one by a hospital physician, and one by a general practitioner. As shown in Table 1 most disorders (7/9) were due to red yeast rice (Monascus purpureus) (n = 4) and liquorice (n = 3) (Glycyrrhiza glabra). In all reports Monascus purpureus was used to treat hypercholesterolaemia, and all events were assessed as ‘probable’, according to the Naranjo probability scale; all cases showed increased concentrations of serum creatinine phosphokinase (CPK) and their onset varied from 2 to 6 months. One of the patients reported previous statin intolerance, while the one who showed the highest increase in CPK (401 IU l−1; normal range 24–195 IU l−1) reported concurrent muscle pain. In the latter case the ADR did not resolve after discontinuation of red yeast rice. Table 1 Reports of myopathies associated with use of herbal drugs A case of rhabdomyolysis was diagnosed after 3 months of liquorice consumption (30–40 g day−1) but signs and symptoms disappeared after dechallenge. Laboratory data were unavailable. Another patient presented with a remarkable increase in CPK (8000 IU l−1) and blood nitrogen (6.0 mg dl−1, normal range: 0.2–6.0 mg l−1) after 20 days of self-administration of a laxative product containing liquorice. At a 6-month follow up, CPK concentrations were still elevated. Causality was assessed as ‘possible’ since the patient had undergone a previous 8-year consumption of simvastatin and lansoprazole, two drugs possibly associated with muscle injury. Although both drugs were stopped several weeks before the onset of rhabdomyolysis, their previous consumption was taken into account when assessing the causality relationship. A case of hypertension, hypokalaemia, hypernatraemia and increased CPK was also reported after 3 months of liquorice juice consumption as self-medication for chronic hypotension. After dechallenge and anti-aldosterone treatment, the patient completely recovered. According to a WHO critical term list, all reports referring to liquorice consumption were classified as ‘serious’ due to hospital admission and two out of three reactions were assessed as ‘probable’. In two cases, symptoms completely resolved after product discontinuation. Major alternative causes of muscle disorders, including alcohol abuse, illicit drug use, infections, metabolic, endocrine or inflammatory diseases were excluded in all seven patients. We can confirm the recent ‘signal’ seen in the medical literature of case reports of muscle disorders associated with red yeast rice and liquorice through our analysis of the Italian national database of adverse reactions to natural health products. All reported cases of ADRs are biologically plausible and supported by preclinical and physiopathological rationale. For instance, chronic or acute liquorice use, through glycyrrhizic acid, is able to inhibit 11β-hydroxysteroid deydrogenase-2 impairing lipid metabolism in muscle cells [3], while Monascus purpureus contains mevalonic acid and Monacolin K, an agent that has the same structure and activity as lovastatin [2, 7]. Although some case reports [4, 8, 9] have already raised this concern, favourable attitudes towards herbal preparations are still strong in industrialized countries [10]. In the majority of the cases reported here, red yeast rice was used to treat dyslipidaemia, often as a self-medication, without a physicians and/or pharmacists supervision. Many patients could therefore be exposing themselves dangerously to the additive effect of herbal and synthetic drugs, such as statins, whose potential adverse effect on muscle is well documented. Moreover, a previous statin intolerance constitutes a critical point for red yeast rice use; this should be taken into account by physicians when suggesting this kind of natural remedy to their patients, as well as by statin-intolerant patients seeking natural alternatives to synthetic drugs, who might be unaware of the real benefit–harm profile of these products.

Two contemporary cases of hepatitis associated with Teucrium chamaedrys L. decoction use: case reports and review of literature.

Abstract:  Teucrium chamaedrys L. is a herbaceous plant common in European woods that has been used for many purposes for centuries. Recently, T. chamaedrys L. has become popular as a slimming decoction without any scientific proof of efficacy notwithstanding its well‐known hepatotoxicity. Hydroalcoholic extracts are currently used as flavourings in the preparation of wines, bitters and liqueurs. Teucrin A and teuchamaedryn A are the major toxic components of the diterpenoid fraction of T. chamaedrys L.

Can Estragole in Fennel Seed Decoctions Really Be Considered a Danger for Human Health? A Fennel Safety Update

Fennel (Foeniculum vulgare Mill.) mature fruit (commonly known as seeds) and essential oil of fennel are widely used as flavoring agents in food products such as liqueurs, bread, cheese, and an ingredient of cosmetics and pharmaceutical products. Moreover fennel infusions are the classical decoction for nursing babies to prevent flatulence and colic spasm. Traditionally in Europe and Mediterranean areas fennel is used as antispasmodic, diuretic, anti-inflammatory, analgesic, secretomotor, secretolytic, galactagogue, eye lotion, and antioxidant remedy and integrator. Topically, fennel powder is used as a poultice for snake bites. In Asian cultures fennel was ingested to speed the elimination of poisons. As one of the ancient Saxon peoples nine sacred herbs, fennel was credited with the power to cure. Fennel was also valued as a magic herb: in the Middle Ages it was draped over doorways on Midsummers Eve to protect the household from evil spirits. Recently because of estragole carcinogenicity, fennel has been charged to be dangerous for humans especially if used as decoction for babies. But this allegation do not consider the remedy is prepared as a matrix of substances, and recent researches confirm that pure estragole is inactivated by many substance contained in the decoction.

Endophytic and rhizospheric bacterial communities isolated from the medicinal plants Echinacea purpurea and Echinacea angustifolia

The Iberian Pyrite Belt, located in Southwestern Spain, represents one of the worlds largest accumulations of mine wastes and acid mine drainages. This study reports the comparative microbial ecology of the water column of Nuestra Señora del Carmen acid pit lake with the extreme acidic Río Tinto basin. The canonical correspondence analysis identified members of the Leptospirillum, Acidiphilium, Metallibacterium, Acidithiobacillus, Ferrimicrobium and Acidisphaera genera as the most representative microorganisms of both ecosystems. The presence of archaeal members is scarce in both systems. Only sequences clustering with the Thermoplasmata have been retrieved in the bottom layer of Nuestra Señora del Carmen and one station of Río Tinto. Although the photosynthetically active radiation values measured in this lake upper layer were low, they were sufficient to activate photosynthesis in acidophilic microorganisms. All identified photosynthetic microorganisms in Nuestra Señora del Carmen (members of the Chlamydomonas, Zygnemopsis and Klebsormidium genera) are major members of the photosynthetic eukaryotic community characterized in Río Tinto basin. This study demonstrates a close relationship between the microbial diversity of Nuestra Señora del Carmen pit lake and the diversity detected in the Río Tinto basin, which underlain the influence of the shared mineral substrates in the microbial ecology of these ecosystems.In this work we analyzed the composition and structure of cultivable bacterial communities isolated from the stem/leaf and root compartments of two medicinal plants, Echinacea purpurea (L.) Moench and Echinacea angustifolia (DC.) Hell, grown in the same soil, as well as the bacterial community from their rhizospheric soils. Molecular PCR-based techniques were applied to cultivable bacteria isolated from the three compartments of the two plants. The results showed that the two plants and their respective compartments were characterized by different communities, indicating a low degree of strain sharing and a strong selective pressure within plant tissues. Pseudomonas was the most highly represented genus, together with Actinobacteria and Bacillus spp. The presence of distinct bacterial communities in different plant species and among compartments of the same plant species could account for the differences in the medicinal properties of the two plants.

Interactions between Natural Health Products and Oral Anticoagulants: Spontaneous Reports in the Italian SurveillanceSystem of Natural Health Products

Introduction. The safety of vitamin K antagonists (VKA) use can be compromised by many popular herbal supplements taken by individuals. The literature reports that 30% of warfarin-treated patients self-medicates with herbs. Possible interactions represent an health risk. We aimed to identify all herbs-oral anticoagulants interactions collected in the Italian database of suspected adverse reactions to “natural health” products. Methods. The Italian database of spontaneous reports of suspected adverse reactions to natural products was analyzed to address herb-VKAs interactions. Results. From 2002 to 2009, we identified 12 reports with 7 cases of INR reduction in patients treated with warfarin (n = 3) and acenocoumarol (n = 4), and 5 cases of INR increase (all warfarin associated). It was reported 8 different herbal products as possibly interacting. Discussion. Our study confirms the risk of interactions, highlighting the difficulty to characterize them and their mechanisms and, finally, prevent their onset. The reported data underline the urgent need of healthcare providers being aware of the possible interaction between natural products and VKA, also because of the critical clinical conditions affecting patients. This is the first step to have the best approach to understand possible INR alterations linked to herb-VKA interaction and to rightly educate patients in treatment with VKA.

Black Cohosh Hepatic Safety: Follow-Up of 107 Patients Consuming a Special Cimicifuga racemosa rhizome Herbal Extract and Review of Literature.

European Medicines Agency (EMEA) and the Committee on Herbal Medicinal Products (HMPC) on July 2006 have released an alert to get European sanitary authorities aware of 42 cases of suspected hepatotoxic reactions in patients consuming Cimicifuga racemosa rhizome. In the public statement EMEA itself considered reliable as hepatotoxic reactions only four cases, on the base of RUCAM score: two were considered possible and two probable. Lacking in almost all of them a precise description of cases, especially a botanical-chemical analysis of the suspected substance, we think there is no real proof of supposed C. racemosa rhizome hepatotoxicity. In our department we administer from about 10 years C. racemosa as special herbal dry extract as single substance or mixed with other medicinal plants at the dose of 500–1000 mg daily, for treatment of menopause related disorders without any reported adverse effect. After EMEAs official signal we have contacted all our patients using a C. racemosa rhizome herbal extract continuously from more than 12 months to verify possible hepatotoxic effects. We followed-up 107 women, and asked them by telephone (33/107) and/or after anamnesis and clinical examination (74/107) to undergo a blood sample examination. In all the patients there was no sign of hepatic disease, or worsening of already altered but stable parameters. We think on the base of these data and current literature C. racemosa rhizome extract should not be considered a potential hepatotoxic substance.

Exploring the Anti-Burkholderia cepacia Complex Activity of Essential Oils: A Preliminary Analysis

In this work we have checked the ability of the essential oils extracted from six different medicinal plants (Eugenia caryophyllata, Origanum vulgare, Rosmarinus officinalis, Lavandula officinalis, Melaleuca alternifolia, and Thymus vulgaris) to inhibit the growth of 18 bacterial type strains belonging to the 18 known species of the Burkholderia cepacia complex (Bcc). These bacteria are opportunistic human pathogens that can cause severe infection in immunocompromised patients, especially those affected by cystic fibrosis (CF), and are often resistant to multiple antibiotics. The analysis of the aromatograms produced by the six oils revealed that, in spite of their different chemical composition, all of them were able to contrast the growth of Bcc members. However, three of them (i.e., Eugenia caryophyllata, Origanum vulgare, and Thymus vulgaris) were particularly active versus the Bcc strains, including those exhibiting a high degree or resistance to ciprofloxacin, one of the most used antibiotics to treat Bcc infections. These three oils are also active toward both environmental and clinical strains (isolated from CF patients), suggesting that they might be used in the future to fight B. cepacia complex infections.