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Severe phototoxic reaction to laser treatment in a patient taking St John's Wort.

Potential patients in the developed world are increasingly turning to treatment with herbs. One of the most popular herbs taken for depression is St John's Wort, which contains the potential photosensitizer hypericin. 'Hypericism' is a term used to describe a state of skin sensitivity to visible light in animals following ingestion of hypericin-containing plants and feed. A patient who developed a severe phototoxic reaction to laser light at 532 nm and also an exaggerated and unexpectedly severe response to pulsed dye laser light at 585 nm is described. It subsequently transpired that the patient was taking St John's Wort at the time of laser treatment.

Anthracenes↗

Mood-enhancing antidepressant St. John's wort inhibits the activation of human immunodeficiency virus gene expression by ultraviolet light.

Ultraviolet (UV) radiation is a potent activator of the human immunodeficiency virus (HIV) gene expression in a HeLa cell clone with stably integrated copies of the HIVcat reporter construct. Recently, we have shown that activation of p38 MAP kinase and NF-kappaB is necessary but not sufficient for triggering efficient HIV gene expression in response to UV. Here we demonstrate that St. John's wort is a potent inhibitor of the UV-induced activation of HIV gene expression in HeLa cells. Stably transfected HIVcat/HeLa cells were preincubated with different amounts (25-100 microl) of St. John's wort or gingko biloba extracts for 30 min, then irradiated with UV (30 J/m2). In contrast to ginkgo biloba, St. John's wort inhibited the UV-induced HIV gene expression in a dose-dependent manner. Furthermore, preincubation with St. John's wort (10, 20, and 30 microl) for 30 min before UV (30 J/m2) irradiation, PMA- and UV-induced NF-kappaB activation was completely blocked, whereas ginkgo biloba did not affect the PMA- and UV-induced NF-kappaB activation in HeLa cells. UV activation of p38 MAP kinase was not inhibited by St. John's wort or by ginkgo biloba. However, we found that p38 MAP kinase and JNK1 and -2 were activated by St. John's wort, but p44/42 MAP kinase was not activated by St. John's wort in HeLa cells. Hypericin an active ingredient in St. John's wort also inhibited the UV activation of HIV gene expression in HeLa cells. These results firmly confirm that St. John's wort is a potent inhibitor of the UV-induced activation of HIV gene expression in HeLa cells.

Anthracenes↗

Analysis and stability of the constituents of artichoke and St. John's wort tinctures by HPLC-DAD and HPLC-MS.

In continuing our investigations on tinctures, which represent both herbal drug preparations and herbal medicinal products, 40% and 60% v/v tinctures of artichoke and St. John's wort were investigated. Artichoke is largely used in hepatic disorders, while St. John's wort is an anti-inflammatory, antidepressant, and healing agent. Both herbal drugs contain various constituents, although the compounds responsible for the main effects have not yet been completely identified. However, caffeoylquinic acids and flavones seem to be of crucial importance for the activity of artichoke, as well as flavonoids, naphthodianthrones, and phloroglucinol derivatives for St. John's wort, and they are used as marker constituents. Thus, quantification of all these constituents was performed using high-performance liquid chromatography-diode array detection (HPLC-DAD) and HPLC--mass spectrometry (MS) analyses with rutin as external standard. In addition the stability of the constituents of these tinctures from accelerated and long-term testing was also evaluated. From the results it was evidenced that constituent content depends on the solvent used for the extraction. The stability was also shown to be very different and seems to be related to the water content of the tinctures.

Chromatography, High Pressure Liquid↗

Herbal product use and menopause symptom relief in primary care patients: a MetroNet study.

OBJECTIVES: The four study objectives were to determine (1) the prevalence of use of four herbal product types promoted to reduce menopause symptoms (phytoestrogens, St. John's wort, Ginkgo biloba, and ginseng) among primary care patients approaching or in menopause, (2) the extent to which women who use these types of herbal products report menopause-related symptoms compared with herbal product nonusers, (3) the frequency of reported symptom reduction after use, and (4) if use was disclosed to their physicians. METHODS: A cross-section of ethnically diverse women 40-55 years of age (35.5% African American, 60.2% Caucasian) who were recruited from eight primary care centers in Michigan to complete a self-report survey. The questionnaire included demographic items, health history, recent use of four herbal product types purported to relieve menopause symptoms and perception of symptom improvement, and interest in additional herbal product information. RESULTS: Of 397 women, 24.9% reported taking, in the previous 6 months, at least one of the four study herbs. Herbal product use did not vary by patient demographics or health characteristics. Herbal product users reported more menopause symptoms than nonusers, and 68% of the users said that the herbs improved their symptoms; 56.4% said that their physician was aware of their herbal product use. CONCLUSIONS: Primary care patients experiencing common menopausal symptoms are likely to use herbal products that are purported to provide menopause symptom relief, and many believe that these products improve their menopausal symptoms. Healthcare providers should be aware of patient's positive attitude, use patterns, and lack of disclosure of use of herbal medicines. Inquiry of herbal product use is another way for physicians to learn about patient self-medication of bothersome symptoms.

Adult↗

Use of St. John's Wort by adolescents with a psychiatric disorder.

Herbal remedies are commonly used for psychiatric problems, but there is virtually no data about the use of these substances by young persons or by patients in treatment. Four adolescents who used St. John's Wort while under psychiatric care are described. Three of the patients had been reluctant to reveal this to their psychiatrist, believing the doctor had no interest in alternative medicine or would disapprove. Patient beliefs that prescribed medication has limitations and that natural products are safe contributed to the use of herbal remedies. The cases raise a number of issues, including the need for clinicians to routinely ask patients about alternative medicine use, to learn more about these treatments, and to discuss these approaches objectively with patients.

Adolescent↗

Open-label pilot study of St. John's wort in adolescent depression.

AIM: Clinical experience suggests the use of alternative remedies, such as St. John's Wort (SJW), in adolescents with affective disorders is increasing. In view of the paucity of documented, well-established, and safe antidepressant medications for children and adolescents, it was important to investigate the potential usefulness of SJW in adolescents with major depressive disorders (MDD). METHODS AND RESULTS: An 8-week, open-label study evaluated the potential efficacy and safety of SJW (300 mg TID) in adolescents with MDD. Twenty-six patients, 12-17 years of age (mean age, 14.8 years) were enrolled in the study. Of the 11 patients who completed the study, 9 patients (82%) showed significant clinical improvement based on Clinical Global Improvement (CGI) change scores (treatment response was indicated by a clinical improvement rating of either very much improved or much improved at the final visit). Of the 15 patients (58%) who did not complete the study, 8 patients were noncompliant and 7 patients were discontinued because of persisting or worsening depression. Of the 8 noncompliant patients, at week 8, 2 patients (25%) remained unchanged, 1 patient (12.5%) was minimally improved, 4 patients (75%) were much improved, and 1 patient (12.5%) was very much improved, based on the CGI change score. CONCLUSION: Preliminary findings suggest that SJW is well tolerated and may be clinically effective in the treatment of some adolescents with mild depression. Controlled trials of SJW in adolescents with MDD are suggested.

Adolescent↗

The nuclear pregnane X receptor regulates xenobiotic detoxification.

The pregnane X receptor (PXR), which is a member of the nuclear receptor family of ligand-activated transcription factors, is an integral component of the body's defense mechanism against toxic xenobiotics. PXR is activated by a broad spectrum of lipophilic xenobiotics including prescription drugs, herbs, pesticides, endocrine disruptors and other environmental contaminants. The promiscuous ligand-binding properties of PXR are facilitated by the large volume and smooth shape of its ligand-binding pocket. PXR binds to DNA as a heterodimer with the 9-cis retinoic acid receptor (RXR) and regulates a large number of genes involved in the detoxification and excretion of toxic substances. Although PXR evolved to protect the body, its activation by various prescription drugs and herbs such as St. John's wort represents the molecular basis for an important class of drug-drug interactions. Assays that detect PXR activation can now be used to predict and prevent these drug-drug interactions.

Animals↗

Effects of St. John's wort on irinotecan metabolism.

St. John's wort (SJW), a widely used herbal product, has been implicated in drug interactions resulting from the induced expression of the cytochrome P450 CYP3A4 isoform. In this study, we determined the effect of SJW on the metabolism of irinotecan, a pro-drug of SN-38 and a known substrate for CYP3A4. Five cancer patients were treated with irinotecan (350 mg/m(2), intravenously) in the presence and absence of SJW (900 mg daily, orally for 18 days) in an unblinded, randomized crossover study design. The plasma levels of the active metabolite SN-38 decreased by 42% (95% confidence interval [CI] = 14% to 70%) following SJW cotreatment with 1.0 micro M x h (95% CI = 0.34 micro M x h to 1.7 micro M x h) versus 1.7 micro M x h (95% CI = 0.83 micro M x h to 2.6 micro M x h) (P =.033, two-sided paired Student's t test). Consequently, the degree of myelosuppression was substantially worse in the absence of SJW. These findings indicate that patients on irinotecan treatment should refrain from taking SJW because plasma levels of SN-38 were dramatically reduced, which may have a deleterious impact on treatment outcome.

Antidepressive Agents↗